Medium-dose Group Research Articles

The effects of antioxidant administration in the early stages of radiation-induced tumorigenesis.

ApcMin/+ mouse was a model mouse for human familial adenomatous polyposis, and irradiation at an early age increases tumors in the small and large intestine. To study the effects of antioxidant administration on tumor incidence after continuous whole-body exposure to gamma rays, ApcMin/+ mice were exposed to a medium-dose-rate, 200mGy/d, from postnatal Day 0 to 21 of age or a high-dose-rate of 0.65Gy/min (total dose 4.2Gy) on postnatal Day 7. The dams and pups were supplied with the N-acetylcysteine (NAC) in drinking water (7g/L), from gestation Day 15 until weaning (21days-old). A significant increase in the number of intestinal tumors were observed in ApcMin/+ mice irradiated with high dose-rate gamma rays as compared with the non-irradiated controls, but there was no significant difference in tumor counts between the non-irradiated controls and the medium-dose rate irradiation groups. NAC administration did not have any significant effect at least at this dose. These results suggest that the supplementation of anti-oxidant at the early stage of tumorigenesis does not suppress the formation of irradiation-induced small intestinal tumors.

The administration of Glycyrrhiza polysaccharides mitigates liver injury in mice caused by mancozeb via the Keap1-Nrf2/NF-κB pathway

The extensive utilization of mancozeb (MCZ) poses environmental pollution risks, threatens human health, particularly hepatotoxicity. Glycyrrhiza polysaccharides (GP) exhibit antioxidant, anti-inflammatory and other biological activities. The aim of this study is to explore the mechanism of liver injury in mice exposed to MCZ and the protective effect of GP on alleviating MCZ induced liver injury. Initially, 70 female mice were divided into 7 groups, and the optimal dose of MCZ induced liver injury in mice was screened by oral administration different doses of MCZ (0, 50, 100, 150, 200, 250 and 300 mg/kg MCZ). The results demonstrated that, compared to the blank control group, as the concentration of MCZ increased, several physiological and biochemical parameters were significantly affected. Specifically, body weight and liver index significantly decreased, while the activities of SOD and CAT also decreased. Additionally, the content of ROS increased, the levels of Keap1 and Nrf2 proteins increased, the mRNA levels of Gpx2 and HO-1decreased, and the mRNA levels of Gstt2, GcLc and NQO1 were upregulated. Based on the test data, select 100mg/kg MCZ as the optimal modeling dose for experimental animals. Sixty female mice were divided into six groups and orally administered: control group A (0.2mL deionized water), model group B (100mg/kg MCZ), positive control group F (100mg/kg MCZ+100mg/kg VC), the high-dose GP group C (100mg/kgMCZ+200mg/kgGP), the medium-dose GP group D (100mg/kg MCZ+150mg/kgGP) and the low-dose GP group E (100mg/kg MCZ+100mg/kgGP). The results showed that compared to the model group, adding GP alleviated the effects of MCZ on body weight, liver index, CAT and SOD activity, MDA content, HO-1, TNF-α, and IL-1β. Additionally, the addition of GP decreased the expression of Keap1, Nrf2, NF-kB, and NQO1, GcLc, and Gstt2 mRNA. GP ameliorated liver vacuolar degeneration, steatosis and nuclear pyknosis ameliorate by MCZ. The results show that MCZ triggers hepatotoxicity via the activation of the Keap1/Nrf2 signaling pathway, whereas GP has the potential to mitigate liver damage caused by MCZ exposure by inhibiting this pathway.

Banxia xiexin decoction prevents the development of gastric cancer.

In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown. To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, in vivo and in vitro experiments. The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments. All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. In vitro cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of EGFR, PIK3CA, IL6, BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression. BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

Immunomodulatory Effects of a Prebiotic Formula with 2'-Fucosyllactose and Galacto- and Fructo-Oligosaccharides on Cyclophosphamide (CTX)-Induced Immunosuppressed BALB/c Mice via the Gut-Immune Axis.

Obejectives: This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Methods: Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. Results: The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as g_Streptomyces and g_Bacillus and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as g_Saccharomyces. The results suggest that 2FGF may enhance immunity via the gut-immune axis. Conclusions: The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway.

Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

Macleaya cordata extract improves egg quality by altering gut health and microbiota in laying hens

This study investigated the effect of Macleaya cordata extract (MCE) on the performance, gut health, and microbiota of laying hens. A total of 192 thirty-wk-old Hyline brown laying hens were randomly divided into 4 treatment groups. The CON group received a basal diet, while the low (MCE250), medium (MCE350), and high (MCE450) dose groups were supplemented with 250, 350, and 450 mg/kg MCE, respectively. The egg weight and Haugh unit demonstrated a linear and quadratic increase with the MCE dose during the initial 4-wk period of the experiment (P < 0.05). Furthermore, the dietary supplementation of MCE led to a significant enhancement in eggshell thickness and Haugh unit at wk 8 and the data showed a statistically significant linear and quadratic increase (P < 0.05). Serum cytokine assay showed that dietary supplementation of MCE led to linear and quadratic increases in IL-4 and IL-10 level (P < 0.05). Dietary supplementation of 350 and 450 mg/kg MCE was observed to result in linear and quadratic increase in serum lysozyme levels (P < 0.05). The addition of MCE to the diet resulted in a linear and quadratic increase in the levels of sIgA in the jejunum and ileum (P < 0.05). In terms of gene expression, the addition of MCE to the diet resulted in linear and quadratic increases in the expression of IL-10, IgA, Serpinb14, Serpinb14B, and OIH (P < 0.05). The expression of jejunal genes pIgR and IL-4 was observed to increase in a linear and quadratic manner, respectively, following the dietary addition of 350 mg/kg MCE and IL-1β decreased in a linear manner (P < 0.05). Moreover, these favorable effects were maximized at medium dosage (350 mg/kg) of MCE addition, and intestinal microbial composition in the control and MCE350 groups was assessed. 350 mg/kg MCE increased the relative abundance of Bryobacter and Parasutterella and decreased the relative abundance of Erysipelatoclostridium in the cecum (P < 0.05). Spearman correlation analysis revealed that Bryobacter, Parasutterella, Skermanella, and Erysipelatoclostridium were associated with nonspecific immune functions (P < 0.05). In conclusion, 350 mg/kg MCE supplementation elevated the immune response, and upregulated the expression of genes related to protein production in eggs, thereby improving egg quality. These effects may be associated with changes in the microbiota, specifically Bryobacter, Parasutterella, and Erysipelatoclostridium.

Oral Administration of Lactiplantibacillus plantarum CCFM8661 Alleviates Dichlorvos-Induced Toxicity in Mice

Dichlorvos (DDVP) is an organophosphorus pesticide commonly used in agriculture for pest control, which may enter the organism from the food chain and cause harm. This study aimed to investigate the mitigation effect of Lactiplantibacillus plantarum CCFM8661 (a strain of the bacteria) on DDVP toxicity. Sixty male mice were randomly divided into five groups including control (saline), model (DDVP), low-dose, medium-dose, and high-dose groups, and alleviating effect was evaluated by determining body weight, pesticide residues, oxidative stress, and inflammation, and by histological analysis. The results showed that compared with the model group, body weight and acetylcholinesterase activity, and SOD, CAT, T-AOC, and GSH levels significantly increased, and serum DDVP content, MDA level, IL-1β, and TNF-α significantly decreased after administration of the L. plantarum CCFM8661. The study demonstrated that L. plantarum CCFM8661 exhibited a significant detoxification effect on pesticide toxicity in mice, providing a theoretical basis for the application of probiotics in mitigating pesticide-induced damage.

Correlation between the nucleic acid load of Bordetella pertussis and clinical features and severity of illness in infants and young children with wooping cough

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children's Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×109/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group (F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups (χ²=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups (χ²=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ²=9.581), the BP-DNA load (6.56 log10 copies/ml, Z=4.004), the WBC count(31.34×109/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ²=36.536), the incidence of wheezing or dyspnea (55.6%, χ²=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ²=26.266), and the incidence of fever (55.6%, χ²=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ²=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×106 copies/ml, WBC count >19.97×109/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×106 copies/ml or WBC counts>19.97×109/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Regulation of Glutamate and γ-Aminobutyric Acid Receptors in Rats with Depression by Sniffing the Essential Oil of Citrus × aurantium L. [Rutaceae

Background Modern research has proved that the volatile oil (VO) of Citrus × aurantium L. [Rutaceae] has the effect of treating depression, but the mechanism of treating depression by sniffing has not been studied. Purpose To study the mechanism of VO on depression. Methods Part I: Except for the blank group, the sniffing group and nasal drip group were continuously administered for 7 days to investigate the optimal administration method. Part II: Except for the blank group, the model, positive group, high, medium, and low dose group of VO were established by chronic unpredictable stress test. The VO was given on the 7th day of modeling for 17 consecutive days. The expression of neurotransmitters and receptors in the brain was determined. The medicinal ingredients in rat brain tissue and blood were detected by gas chromatography–mass spectrometry (GC–MS). Results Compared with nasal drip, sniffing administration has less irritation to the nasal mucosa. The VO could reduce the forced swimming immobility time, adjust the activity state, increase the content of γ-aminobutyric acid (GABA), reduce the content of glutamate, and upregulate the expression of GABAα1, GABAγ2, and their mRNA. The main pharmaceutical component is d-limonene. Conclusion d-limonene in VO upregulates GABAα1, GABAγ2 expression to treat depression.

High-Dose TXA Is Associated with Less Blood Loss Than Low-Dose TXA without Increased Complications in Patients with Complex Adult Spinal Deformity.

Tranexamic acid (TXA) is commonly utilized to reduce blood loss in adult spinal deformity (ASD) surgery. Despite its widespread use, there is a lack of consensus regarding the optimal dosing regimen. The aim of this study was to assess differences in blood loss and complications between high, medium, and low-dose TXA regimens among patients undergoing surgery for complex ASD. A multicenter database was retrospectively analyzed to identify 265 patients with complex ASD. Patients were separated into 3 groups by TXA regimen: (1) low dose (<20-mg/kg loading dose with ≤2-mg/kg/hr maintenance dose), (2) medium dose (20 to 50-mg/kg loading dose with 2 to 5-mg/kg/hr maintenance dose), and (3) high dose (>50-mg/kg loading dose with ≥5-mg/kg/hr maintenance dose). The measured outcomes included blood loss, complications, and red blood cell (RBC) units transfused intraoperatively and perioperatively. The multivariable analysis controlled for TXA dosing regimen, levels fused, operating room time, preoperative hemoglobin, 3-column osteotomy, and posterior interbody fusion. The cohort was predominantly White (91.3%) and female (69.1%) and had a mean age of 61.6 years. Of the 265 patients, 54 (20.4%) received low-dose, 131 (49.4%) received medium-dose, and 80 (30.2%) received high-dose TXA. The median blood loss was 1,200 mL (interquartile range [IQR], 750 to 2,000). The median RBC units transfused intraoperatively was 1.0 (IQR, 0.0 to 2.0), and the median RBC units transfused perioperatively was 2.0 (IQR, 1.0 to 4.0). Compared with the high-dose group, the low-dose group had increased blood loss (by 513.0 mL; p = 0.022) as well as increased RBC units transfused intraoperatively (by 0.6 units; p < 0.001) and perioperatively (by 0.3 units; p = 0.024). The medium-dose group had increased blood loss (by 491.8 mL; p = 0.006) as well as increased RBC units transfused intraoperatively (by 0.7 units; p < 0.001) and perioperatively (by 0.5 units; p < 0.001) compared with the high-dose group. Patients with ASD who received high-dose intraoperative TXA had fewer RBC transfusions intraoperatively, fewer RBC transfusions perioperatively, and less blood loss than those who received low or medium-dose TXA, with no differences in the rates of seizure or thromboembolic complications. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comprehensive combined analysis of physician-initiated phase II and III clinical trials on a cultured human corneal endothelial cell product for treating bullous keratopathy.

To evaluate the efficacy and safety of a cultured human corneal endothelial cell (cHCEC) product in eyes with bullous keratopathy (BK). Combined analysis of multicenter phase II and III clinical trials. This analysis involved 15 BK eyes in the phase II trial and 12 BK eyes in the phase III trial that underwent cHCEC transplant therapy. Safety was assessed in all the cases. Efficacy was assessed in 17 cases with exclusion of the low- and medium-dose groups in the phase II trial. The primary endpoint was a corneal endothelial cell density of 1000 cells/mm2 or more at 24 weeks post-transplant, which was attained in 94.1% of the eyes (16 of 17), with a 95% CI of 71.3-99.9%. Additionally, 82.4% of the eyes (14 of 17) met the secondary endpoint of reduction in corneal thickness to less than 630 µm without corneal epithelial edema within the same time frame, with a 95% CI of 56.6-96.2%. The mean decrease in corneal thickness from baseline to 24 weeks post-transplant was -187.4 µm (95% CI, -240.2 µm to -134.5 µm). Furthermore, all the eyes exhibited improvement in best-corrected visual acuity from baseline to 24 weeks post-transplant (95% CI, 80.5-100.0%). By 24 weeks post-transplant, 88.9% of the patients (24 of 27) had experienced adverse events, which were mostly local, mild, and transient. The cHCEC product of this study reconstitutes the corneal endothelial layer with high cellular density and restores corneal thickness and improves visual acuity.

Low-dose tolvaptan to control disease progression in Chinese patients with autosomal dominant polycystic kidney disease: a retrospective cohort study.

Tolvaptan has been shown to be effective in the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, there is limited evidence regarding optimal dosing and its application within the Chinese population. In this study, we aimed to determine whether a lower tolvaptan dose could effectively control ADPKD in Chinese patients. This retrospective, single-center cohort study was conducted in a real-world setting and included all patients newly diagnosed with rapidly progressive ADPKD who initiated tolvaptan treatment and maintained it for at least 12 months. Data were collected at baseline and at 1, 2, 4, 8, and 12 months after treatment initiation. Patients began with morning/evening tolvaptan doses of 7.5 mg/7.5 mg, and the dose was subsequently adjusted based on effectiveness and tolerability. The patients were categorized by baseline estimated glomerular filtration rate (eGFR) and final daily tolvaptan dose. Changes in eGFR and other key physiological indicators after treatment were compared within each group. The study included 43 patients with ADPKD, of whom 20 were female, with a median age of 34.3 years (range, 16-85 years). At 12 months, eGFR improved by 5.48 mL/min/1.73 m2 [95% confidence interval (CI): 2.68-8.29] (P<0.001) compared to baseline. Significant improvements were observed in patients with baseline eGFR levels of 30-59, 60-89, and ≥90 mL/min/1.73 m2 (P=0.007, 0.045, and 0.02, respectively), as well as in medium and high dose groups (P=0.002 and 0.02, respectively). At 12 months, the annual height-adjusted total kidney volume (HtTKV) growth slope decreased by -0.17 %/year (95% CI: -0.33 to -0.01) (P=0.04). Significant decreases were observed in patients with an eGFR of 30-59 mL/min/1.73 m2 (P=0.008) and in the medium dose group (P=0.03). Thirst was reported in 22 (51.2%) patients, all of whom experienced mild symptoms. No liver-associated adverse events were noted. Tolvaptan is well tolerated at low initial doses in Chinese patients with ADPKD. Significant improvements in eGFR and reduced HtTKV growth were observed in the overall population and across various baseline eGFR and final dose groups.

Yiqi Yangxue formula inhibits cartilage degeneration in knee osteoarthritis by regulating LncRNA-UFC1/miR-34a/MMP-13 axis

Ethnopharmacological relevanceKnee osteoarthritis (KOA) is a prevalent and disabling clinical condition affecting joint structures worldwide. The Yiqi Yangxue formula (YQYXF) is frequently prescribed in clinical settings for the treatment of KOA. Existing research has primarily focused on alterations in drug metabolism, with limited investigation into the epigenetic effects of YQYXF, particularly in relation to non-coding RNA. Aim of the studyExploring the effects of YQYXF on critical factors of long chain non-coding RNA UFC1/miR-34a/matrix metalloproteinase-13 (MMP-13) axis and their interrelationships. MethodsUHPLC-QE-MS technology was used to identify the YQYXF ingredients in rat serum. KEGG and GO analysis were performed on the targets of blood components acting on KOA using a database. Simultaneously, a protein interaction network was constructed using target proteins and metabolites to identify the core components and key pathways of YQYXF. The KOA rat model was established using an improved Hulth method. SPF SD rats were randomly divided into normal group, sham surgery group, model group, celecoxib capsules group (18 mg/kg), YQYXF low, medium and high dose groups (4.6g/kg, 9.2g/kg, 18.4g/kg). Observe the synovial and cartilage tissues of rats using pathological methods. RT-PCR was used to detect the levels of UFC1, miR-34a, and MMP-13 in cartilage. Immunohistochemistry was used to detect the levels of MMP-13 and ADAMTS-5 in cartilage. ELISA method was used to detect the levels of MMP-13 and ADAMTS-5 in serum. In addition, we further validated the regulation of crucial factor expression levels of UFC1/miR-34a/MMP-13 axis in rat chondrocytes and degenerative chondrocytes of KOA patients by YQYXF, providing a basis for its treatment of KOA. ResultsThe compounds that YQYXF enters the bloodstream mainly contain flavonoids and phenylpropanoid compounds. The core components that act on OA include quercetin, fisetin, and demethylweldelolactone. The main target pathways are the IL-17 signaling pathway, lipid and atherosclerosis, cellular sensitivity, inflammatory mediator regulation of TRP channels, TNF signaling pathway, relaxin signaling pathway and C-type lectin receptor signaling pathway. YQYXF inhibited the expression of miR-34a and MMP-13 mRNA, and reduced the protein levels of MMP-13 and ADAMTS-5. In vitro studies have confirmed that 20% YQYXF serum promoted UFC1 and reduce miR-34a levels. In addition, miR-34a in sh-UFC1+10% YQYXF serum and sh-UFC1+20% YQYXF serum groups significantly decreased compared to the sh-UFC1 group. ConclusionThe anti-KOA cartilage degeneration effect of YQYXF might be related to inhibiting cell apoptosis and promoting cell proliferation, which regulated the lncRNA-UFC1/miR-34a/MMP-13 axis.

Haizao–Gancao herb pair ameliorates propylthiouracil-induced goiter by regulating the Beclin1-mediated autophagy

Ethnopharmacological relevanceHaizao, Sargassum, is widely used to treat goiter. Gancao, Glycyrrhizae radix et rhizome, is renowned for reducing toxicity or increasing effects in traditional Chinese medicine. As a classic herb pair, Haizao–Gancao (HG) is a commonly used and effective combined therapy for goiter. The underlying biological mechanisms of HG on goiter is still unclear. Aim of the studyTo explore the effect of HG on goiter, employing molecular docking combined with experimental validation to elucidate the molecular mechanism. Materials and methodsThe rat goiter model was created by gavageing propylthiouracil (PTU) intragastrically for a duration of 14 days. The rats had been separated into six groups: control, model, euthyrox, HG high-dose (HG-H), medium-dose (HG-M) and low-dose (HG-L) group. Based on general observations (such as the rats' living status, body weight, and rectal temperature), the relative weight of the thyroid, thyroid function, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM) to view the pathological variations of the thyroid glands, the effect of HG was evaluated. Discovered the chemical composition of HG by UPLC-MS/MS and the possible targets were predicted adopting several databases. Next, we explored their pharmacological mechanisms using molecular docking and validated key targets using western blotting (WB) and co-immunoprecipitation (Co-IP). ResultsHG significantly increased the levels of triiodothyronine(T3), free triiodothyronine (FT3), free thyroxine (FT4), gained body weight and reduced tumescent thyroid glands in PTU-induced rats. The model group pathological changes such as uneven size, irregular shape and disordered arrangement of follicular epithelial cells occurred. However, HG groups thyroid follicles and epithelial cells appeared apparently normal. A variety of characteristic changes of autophagic vesicles appeared in the HG groups as opposed to the model group. In conclusion, the HG-L showed the best therapeutic effect. By UPLC-MS/MS, the major chemical components of HG were identified. The result revealed that HG contained flavonoids, alkaloids, organic acids, phenolic acidsand and terpenoids, etc. The molecular docking results of formononetin and naringenin and Beclin1 protein showed a high interaction of -5.38 kcal/mol and -5.25 kcal/mol. This implies that formononetin and naringenin may have a therapeutic effect in goiter rats by controlling the Beclin1-mediated autophagy. Western Blot (WB) and co-immunoprecipitation (Co-IP) results showed that HG can disrupt Beclin1/class III phosphatidylinositol 3-kinase(PI3KC3) binding and promote Beclin1/B-cell leukemia/lymphoma-2(Bcl-2) complex formation. Taken together, results demonstrate that autophagy inhibition via reducing Beclin1/PI3KC3 formation and increasing Beclin1/Bcl-2 binding activity. ConclusionsHG ameliorates propylthiouracil-induced goiter by regulating the Beclin1-mediated autophagy, thus promoting the autophagy of thyroid cells.

Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.

Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis. The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1β and TNF-a expression in skin tissues. Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1β, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway. DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

Ameliorative Effect of Hedysarum polybotrys Polysaccharide on Neural Tissue Fibrosis in Diabetic Peripheral Neuropathy Mice and its Mechanisms

Objective: This study aimed to investigate the role of Hedysarum polybotrys polysaccharide (HPS) in ameliorating neural tissue fibrosis in diabetic peripheral neuropathy (DPN) mice. Methods: Fifty DPN mice were selected and randomly divided into five groups (n = 10), which were the model group, positive control group (receiving only 4 mg/(kg-d) of α-lipoic acid), high-dose HPS group (200 mg/(kg-d) of HPS was given per day), medium-dose HPS group (100 mg/(kg-d) of HPS was given per day), and low-dose HPS group (50 mg/(kg-d) of HPS given daily). In addition, non-diabetic C57BL/6 wild-type mice were selected as the normal group (n = 10). The expression levels of Keap1 and Nrf2 proteins and their mRNAs in the sciatic nerve tissues of mice in each group were analyzed by Western blot technique and real-time fluorescence quantitative PCR. Results: Compared with the normal group, the expression of Keap1 protein and mRNA was increased, while the expression of Nrf2 protein and mRNA was decreased in the sciatic nerve of mice in the model group (P &lt; 0.05). Compared with the model group, Keap1 protein and mRNA expression decreased, while Nrf2 protein and mRNA expression increased in the control and high and medium dose HPS groups of mice (P &lt; 0.05). Conclusion: HPS may inhibit fibrosis of neural tissue and ameliorate nerve injury in DPN mice by regulating the Keap1/Nrf2 signaling pathway. This effect was associated with enhanced antioxidant capacity, promotion of Nrf2 activation, and increased antioxidant gene expression by HPS. Therefore, HPS has a potential therapeutic value to ameliorate DPN-associated nerve injury.

Study the Physiological Effects of Palm Heart Extract (PHE) on some Cardiac, Hepatic Enzymes, and Reproductive Hormones in Male Rats

Background: For a long time, researchers have extensively studied the health advantages of natural products derived from plants. Objective: The main goal of this study is to investigate the effects of palm heart extract (PHE) on the lipid profile and various parameters of the heart, liver, and reproductive system in male rabbits. Methods: The male rabbits were divided into four groups by chance; one group was given a standard diet for comparison, while the other three received a PHE supplement. The control group did not get any treatment while three groups were given medium to high doses of PHE daily for 8 weeks. Troponin and lipid profile levels were assessed for health indicators, while liver enzyme levels (ALT, AST, ALP) and total bilirubin were analyzed to evaluate liver function. Furthermore, hormone levels such as testosterone, LH (luteinizing hormone), and FSH (follicle stimulating hormone) were also observed during the entire study period. Outcomes: Lipid profile parameters, including cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), and high density lipoprotein cholesterol (HDL), were assessed before and after the intervention period. Results: The results indicated a reduction in TC and LDL levels in the treatment group compared to the control group was statistically significant (p &lt; 0.05). Nonetheless, there were no changes observed in the levels of TG and HDL in both groups, with a p-value greater than 0.05. These results indicate that heart palm water extract might have the ability to lower lipid levels, especially in decreasing total cholesterol and LDL levels. Testosterone levels showed a small drop in the high dose group when compared to the control group, although there was no statistical significance (p &gt; 0.05). LH levels did not significantly decrease in the medium dose group compared to the control group (p &lt; 0.05). There were no notable variations in FSH levels among the groups (p &lt; 0.05). In conclusion, male rabbits showed reduced troponin levels in a dose-dependent manner, indicating potential cardioprotective effects of HDP extract. The administration of HDP extract did not have any impact on liver function. Although reproductive hormone levels varied, additional research is required to understand the effects of heart palm extract on male reproductive health.

The impact of Codonopsis Pilosulae and Astragalus Membranaceus extract on growth performance, immunity function, antioxidant capacity and intestinal development of weaned piglets.

The objective of this study was to examine the impact of Codonopsis pilosula and Astragalus membranaceus extract (CA) on the growth performance, diarrhea rate, immune function, antioxidant capacity, gut microbiota, and short-chain fatty acids (SCFAs) in weaned piglets. A total of forty-eight 31-day-old weaned piglets, were divided into four groups randomly based on the treatment type: control group (CON), low dose group (LCA, 0.5% CA), medium dose group (MCA, 1.0% CA), and high dose group (HCA, 1.5% CA), and were fed for a duration of 28 days. On the morning of the 1st and 29th day, the piglets were assessed by weighing them on an empty stomach, recording their daily feed intake and diarrhea rate. CA increased the average daily weight gain and reduced F/G without significant differences, and the diarrhea rate was reduced in the LCA and MCA groups. Furthermore, the levels of T-AOC, SOD, GSH-Px, and MDA were increased. The levels of T-AOC in the LCA group and the MCA group, SOD in the MCA group, and GSH-Px in the HCA group were significantly higher compared with the CON group (p < 0.05). Additionally, CA significantly increased IgM, IgG, and IgA levels (p < 0.05). The results of gut microbiota analysis showed that the bacterial population and diversity of faeces were changed with the addition of CA to basal diets. CA increased the abundance of the beneficial bacterial Firmicutes and Lactobacillus. Additionally, Compared with the CON group, CA significantly increased the SCFAs content of weaned piglets (p < 0.05). CA can alleviate oxidative stress, improve immunity and antioxidant capacity, increase the abundance of beneficial bacteria, and the content of SCFAs for improving the intestinal barrier of piglets, thus promoting growth and reducing diarrhea rate in weaned piglets.

Research on ameliorating pulmonary fibrosis in silicosis mice of Cordyceps cicadae polysaccharides

Objective: A mouse silicosis model was constructed by injecting silicon dioxide (SiO(2)) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods: In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO(2) suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results: The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased (P<0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue (P<0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased (P<0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue (P<0.05) . Conclusion: The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO(2) particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into five groups (n=120 each): negative control; positive control (3mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.