RE Group Research Articles

Dose‒response effects of resistance exercise on ameliorating cravings and executive functions in individuals with methamphetamine use disorders

PurposeResistance exercise (RE) can acutely benefit symptoms in individuals with methamphetamine use disorder (MUD), though the optimal dose has not yet been established. We aimed to determine the dose response relationship between RE intensity and cue-elicited cravings and executive functions in individuals with MUD. MethodsA total of 128 male participants with MUD (34.73 ± 5.65) were randomly assigned to the low-intensity (30%–35%1-RM) RE group (LREG), moderate-intensity (55%–60%1-RM) RE group (MREG), high-intensity (75%–80%1-RM) RE group (HREG), or control group (CONG). Cravings based on the cue-reactivity paradigm were measured before, immediately after, and 40 min after acute RE, and inhibitory control, working memory, and cognitive flexibility were measured before and after acute RE. ResultsImmediately after and 40 min after RE, the Δcue-elicited cravings of the MREG from baseline was significantly more negative than that of the LREG and CONG. Trend analyses revealed a U-shaped dose‒response curve for RE intensity and Δcue-elicited cravings, indicating that moderate-intensity RE had the greatest ameliorating effect on cue-elicited cravings. Δinhibitory control and Δworking memory scores increased only in the MREG, and Δcognitive flexibility scores significantly increased in all RE groups. Trend analyses revealed a cubic curvilinear relationship between RE intensity and inhibitory control and a quadratic curvilinear relationship with working memory and cognitive flexibility. ConclusionRE proved effective in diminishing cue-elicited cravings and enhancing executive functions. A significant dose‒response relationship existed among RE intensity, cue-elicited cravings and executive function, and moderate-intensity RE had a more pronounced ameliorative effect on individuals with MUD.

Homeostatic changes of trace elements in diazinon toxicity in rat model: The beneficial role of resveratrol

Background and objectivesDiazinon (DZN) is a cholinesterase inhibitor widely used to relieve agricultural pests and upgrade the productivity of crops. Resveratrol (Res), as a phenolic plant compound, has a protective role against free radicals. This study intended to evaluate the impacts of Res on homeostatic disturbances induced by DZN in rats. MethodTwenty-four Wistar rats (4 weeks) were randomly distributed into four groups of six animals each. The first group (control group) received corn oil. The second group (Res group) received orally Res (20 mg/kg. The third group (DZN group) received the oral DZN (70 mg/kg); the fourth group (Res plus DZN group) was treated simultaneously with DZN (70 mg/kg) and Res (20 mg/kg); for a period of 5 weeks. The serum, liver, kidney, and heart levels of the Copper (Cu), zinc (Zn), iron (Fe), selenium (Se), and magnesium (Mg) as main trace elements are measured. ResultsDZN treatment decreased significantly serum, liver, kidney, and heart levels of Cu, Zn, Fe, Se, and Mg in comparison with the control group. Res administration enhanced serum, liver, kidney, and content of heart elements compared to the DZN group. ConclusionsThese results suggested that Res could ameliorate the homeostatic imbalance induced by DZN. Res had a protective effect against DZN-provoking heart, renal, and hepatic toxicity in animal models.

Aerobic Training and Ointment Effect on range of motion, von Willebrand factor, vascular endothelial factor and Femoral Artery Hemodynamics in Joint Contracture: A Rat Model.

Using a rat model, we investigated the effect of multidisciplinary rehabilitation, including aerobic training and ointment, on the ROM, vWF, VEGF content, and femoral artery hemodynamics in rats with joint contracture. A total of 44 Wistar rats were divided into the normal control group (NC, eight rats) and the experimental group (EG). A joint contracture model was established for the rats in the EG group by an external fixator. After fixator removal, 32 rats are further divided into the MC, SC, RE, and SR groups (n = 8). Before and after the 42day intervention, the ROM, vWF, VEGF, PS, ED, and RI were measured using X-ray imaging, ELISA, and color Doppler ultrasound, respectively. After fixator removal, ROM for EG group was lower than that of the NC group (p < .01). After the intervention, ROM for the SR, RE, and SC groups was improved. The ROM for the SR group reached a similar value for NC group. vWF and VEGF levels in SR group were lower than in the MC, SC, and RE groups (p < .05), and had a similar value to the NC groups. PS value for SR and RE groups was higher than the MC and SC groups. The RI value for SR group was higher than that of NC and MC groups. Multidisciplinary rehabilitation used in this study can treat joint contracture synergistically. It improves the ROM of the joint, reduces the content of vWF and VEGF, and improves the femoral artery hemodynamics.

Application of neutrophil-lymphocyte ratio and red blood cell distribution width in diabetes mellitus complicated with heart failure

BACKGROUND Accumulating clinical evidence has shown that diabetes mellitus (DM) is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events. AIM To explore the value of the combined determination of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the early diagnosis and prognosis evaluation of DM complicated with heart failure (HF). METHODS We retrospectively analyzed clinical data on 65 patients with type 2 DM (T2DM) complicated with HF (research group, Res) and 60 concurrent patients with uncomplicated T2DM (control group, Con) diagnosed at Zhejiang Provincial People’s Hospital between January 2019 and December 2021. The NLR and RDW values were determined and comparatively analyzed, and their levels in T2DM + HF patients with different cardiac function grades were recorded. The receiver operating characteristic (ROC) curves were plotted to determine the NLR and RDW values (alone and in combination) for the early diagnosis of HF. The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated. RESULTS Higher NLR and RDW levels were identified in the Res vs the Con groups (P &lt; 0.05). The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group, with marked differences in their levels among patients with grade II, III, and IV HF (P &lt; 0.05). ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915, a sensitivity of 76.9%, and a specificity of 100% for the early diagnosis of HF. Furthermore, HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events. CONCLUSION NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF, and their joint detection was beneficial for improving diagnostic efficiency. Additionally, NLR and RDW values were directly proportional to patient outcomes.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer

ObjectiveEndometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated.MethodsThe target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug–disease–target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS.ResultsA total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened.ConclusionRes has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Analysis of the Correlation Between Dynamic Characteristics and Symptoms of Gastroesophageal Reflux Disease.

To investigate the esophageal motility characteristics of gastroesophageal reflux disease (GERD) and their relationship with symptoms. We examined 101 patients diagnosed with GERD by endoscopy and divided them into 3 groups as follows: nonerosive reflux disease (NERD), reflux esophagitis, and Barrett esophagus. Esophageal high-resolution manometry and the GERD Questionnaire were used to investigate the characteristics of esophageal dynamics and symptoms. In addition, the reflux symptom index was completed and the patients were divided into 7 groups according to symptoms. We then determined the correlation between dynamic esophageal characteristics and clinical symptoms. Upper (UES) and lower (LES) esophageal sphincter pressures and the 4-second integrated relaxation pressure in the RE group were lower than those in the NERD group. The 4-second integrated relaxation pressure in the Barrett esophagus group was also lower than that in the NERD group. In the analysis of extraesophageal symptoms, high-resolution manometry showed significant differences in UES pressures among all groups. Further subgroup analysis showed that compared with the group without extraesophageal symptoms, the UES pressure of the groups with pharyngeal foreign body sensation, throat clearing, and multiple extraesophageal symptoms was lower. As GERD severity increases, motor dysfunction of the LES and esophageal body gradually worsens, and the LES plays an important role in GERD development. Decreased UES pressure plays an important role in the occurrence of extraesophageal symptoms, which is more noticeable in patients with pharyngeal foreign body sensation and throat clearing.

Reserpine-induced rat model for depression: Behavioral, physiological and PET-based dopamine receptor availability validation

BackgroundReserpine (RES), a Vesicular Monoamine Transporter 2 (VMAT2) inhibitor agent, has been used in preclinical research for many years to create animal models for depression and to test experimental antidepressant strategies. Nevertheless, evidence of the potential use and validity of RES as a chronic pharmacological model for depression is lacking, and there are no comprehensive studies of the behavioral effects in conjunction with molecular outcomes. MethodsExperiment 1. Following baseline behavior testing sensitive to depression-like phenotype and locomotion (Phase 1), 27 Sprague-Dawley (SD) rats received i.p. either vehicle solution (0.0 mg/kg), low (0.2 mg/kg) or high (0.8 mg/kg) RES dose for 20 days using a pre-determined schedule and reassessed for behavioral phenotypes (Phase 2). After 10 days washout period, and a final behavioral assessment (Phase 3), the brains were collected 16 days after the last injection for mRNA-expression assessment. Experiment 2. In a similar timetable as in Experiment 1 but without the behavioral testing, 12 SD rats underwent repetitive dopamine D2/3 receptor PET scanning with [18F]DMFP following each Phase. The binding potential (BPND) of [18F]DMFP was quantified by kinetic analysis as a marker of striatal D2/3R availability. Weight and welfare were monitored throughout the study. ResultsSignificant, dose-dependent weight loss and behavioral deficits including both motor (hypo-locomotion) and non-motor behavior (anhedonia, mild anxiety and reduced exploration) were found for both the low and high dose groups with significant decrease in D2R mRNA expression in the accumbal region for the low RES group after Phase 3. Both RES treated groups showed substantial increase in [18F]DMFP BPND (in line with dopamine depletion) during Phase 2 and 3 compared to baseline and Controls. ConclusionsThe longitudinal design of the study demonstrated that chronic RES administration induced striatal dopamine depletion that persisted even after the wash-out period. However, the behavior phenotype observed were transient. The data suggest that RES administration can induce a rodent model for depression with mild face validity.

Biology of tongue coating in different disease stages of RA and its value in disease progression

ObjectiveTo assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). MethodsA total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3–V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. ResultsSignificant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. ConclusionThe results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

Cytokine profile in peripheral blood mononuclear cells differs between embryo donor and potential recipient sows.

Pregnancy success relies on the establishment of a delicate immune balance that requires the early activation of a series of local and systemic immune mechanisms. The changes in the immunological profile that are normally occurring in the pregnant uterus does not take place in cyclic (non-pregnant) uterus, a fact that has been widely explored in pigs at the tissue local level. Such differences would be especially important in the context of embryo transfer (ET), where a growing body of literature indicates that immunological differences at the uterine level between donors and recipients may significantly impact embryonic mortality. However, whether components of peripheral immunity also play a role in this context remains unknown. Accordingly, our hypothesis is that the immune status of donor sows differs from potential recipients, not only at the tissue local level but also at the systemic level. These differences could contribute to the high embryonic mortality rates occurring in ET programs. In this study differences in systemic immunity, based on cytokine gene expression profile in peripheral blood mononuclear cells (PBMCs), between embryo-bearing donor (DO group; N = 10) and potential recipient sows (RE group; N = 10) at Day 6 after the onset of the estrus were explored. Gene expression analysis was conducted for 6 proinflammatory (IL-1α, IL-1β, IL-2, GM-CSF, IFN-γ, and TNF-α) and 6 anti-inflammatory (IL-4, IL-6, IL-10, IL-13, TGF-β1, and LIF) cytokines. All cytokines were overexpressed in the DO group except for IL-4, suggesting that stimuli derived from the insemination and/or the resultant embryos modify the systemic immune profile in DO sows compared to RE (lacking these stimuli). Our results also suggest that certain cytokines (e.g., IL-1α and IL-1β) might have a predictive value for the pregnancy status.

Taurohyocholic acid acts as a potential predictor of the efficacy of tyrosine kinase inhibitors combined with programmed cell death-1 inhibitors in hepatocellular carcinoma.

Background and aims: Tyrosine kinase inhibitors (TKIs) combined with programmed cell death protein-1 (PD-1) have significantly improved survival in patients with unresectable hepatocellular carcinoma (uHCC), but effective biomarkers to predict treatment efficacy are lacking. Peripheral blood bile acids (BAs) are associated with tumor response to therapy, but their roles in HCC remain unclear. Methods: This retrospective study included HCC patients who received first-line TKIs combined with PD-1 inhibitors treatment (combination therapy) in our clinical center from November 2020 to June 2022. The aim of this study was to analyze the changes in plasma BA profiles before and after treatment in both the responding group (Res group) and the non-responding group (Non-Res group). We aimed to explore the potential role of BAs in predicting the response to combination therapy in HCC patients. Results: Fifty-six patients with HCC who underwent combination therapy were included in this study, with 28 designated as responders (Res group) and 28 as non-responders (Non-Res group). There were differences in plasma BA concentrations between the two groups before systemic therapy. Plasma taurohyocholic acid (THCA) levels in the Res group were significantly lower than those in the Non-Res group. Patients with low levels of THCA exhibited superior median progression-free survival (7.6 vs. 4.9months, p = 0.027) and median overall survival (23.7 vs. 11.6months, p = 0.006) compared to those of patients with high levels of THCA. Conclusion: Peripheral blood BA metabolism is significantly correlated with combination therapy response and survival in patients with HCC. Our findings emphasize the potential of plasma BAs as biomarkers for predicting combination therapy outcomes and offering novel therapeutic targets for modulating responses to systemic cancer therapy.

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge.

Increasing evidence indicates that maternal exposure to oxidized soybean oil (OSO) causes damage to the mother and offspring. The antioxidant resveratrol (Res) has a variety of health benefits. However, the protective effect of Res on mitigating offspring damage after maternal exposure to OSO and its mechanism remains unclear. Therefore, this study aimed to investigate the effect of Res on hepatic fatty acid metabolism and the jejunal barrier in suckling piglets after maternal OSO exposure. A total of 18 sows in late gestation were randomly assigned to three treatments. The sows were fed with a fresh soybean oil (FSO) diet, an OSO diet, or the OSO diet supplemented with 300 mg/kg Res (OSO + Res), respectively. The results showed that maternal supplementation of Res restored the mRNA levels of genes related to fatty acid metabolism and increased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in suckling piglets' livers under the OSO challenge. Moreover, the OSO + Res group restored the mRNA levels of occludin and claudin 4 in suckling piglet jejunum compared with the results of the OSO challenges. In summary, supplementation with Res improves hepatic fatty acid metabolism and intestinal barrier function of suckling piglets after maternal OSO challenge during late gestation and lactation.

Resveratrol Inhibits T-acute Lymphoblastic Leukemia in Mice by Regulating Notch1 Signaling Pathway

To observe the effect of resveratrol (Res) on T-acute lymphoblastic leukemia (T-ALL) mice, and further explore its mechanism on Notch1 signaling pathway. Twenty-five 6-8 weeks old female C57BL/6 mice were randomly divided into control group, T-ALL group and Res group. Res group was further divided into low-Res, middle-Res and high-Res group. The percentage of leukemia cells in peripheral blood and spleen cell suspension were detected by flow cytometry and Wright-Giemsa staining, pathological morphology of spleen and bone marrow tissues were observed by HE staining, the expression levels of Notch1, Hes-1, c-Myc, miR-19b and PTEN mRNA in spleen tissue were detected by RT-qPCR, and the protein levels of Notch1, Hes-1, c-Myc, p-PTEN and PTEN were detected by Western blot. Compared with control group, the leukemia cells in peripheral blood of mice in T-ALL group were markedly increased, accompanied by diffuse infiltration of leukemia cells in spleen and bone marrow tissues, the mRNA levels of Notch1, Hes-1, c-Myc, miR-19b and the protein levels of Notch1, Hes-1, c-Myc were increased (P <0.01), while the expression of PTEN mRNA and protein were significantly decreased in the spleen tissue of T-ALL mice (P <0.01). The above indicators in the H-Res group were reversed compared with T-ALL group after administration of resveratrol. Resveratrol may play a role in anti T-ALL by inhibiting Notch1 signaling pathway in mice.

Mechanism of resveratrol in protecting ovary in poor ovarian response mice by regulating Hippo signaling pathway

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model. After modeling, the low-and high-dose Res groups were continuously treated with drugs by gavage for two weeks, while the blank group and the model group received an equal volume of 0.9% saline solution by gavage. Ovulation was induced in all groups on the day following the end of treatment. Finally, 12 female mice were randomly selected from each group, and the remaining eight female mice were co-housed with male mice at a ratio of 1∶1. Changes in the estrous cycle of mice were observed using vaginal cytology smears. The number of ovulated eggs, ovarian wet weight, ovarian index, and pregnancy rate of mice were measured. The le-vels of anti-Mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in serum were determined using enzyme-linked immunosorbent assay(ELISA). Ovarian tissue morphology and ovarian cell apoptosis were observed using hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining, respectively. The protein expression levels of yes-associated protein(YAP) 1 and transcriptional coactivator with PDZ-binding motif(TAZ) were detected by immunohistochemistry(IHC), while the changes in protein expression levels of mammalian sterile 20-like kinase(MST) 1/2, large tumor suppressor(LATS) 1/2, YAP1, TAZ, B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were determined by Western blot. The results showed that compared with the blank group, the model group had an increased rate of estrous cycle disruption in mice, a decreased number of normally developing ovarian follicles, an increased number of blocked ovarian follicles, increased ovarian granulosa cell apoptosis, decreased ovulation, reduced ovarian wet weight and ovarian index, increased serum FSH and LH levels, decreased AMH and E_2 levels, decreased protein expression levels of YAP1 and TAZ in ovarian tissues, increased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and decreased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Additionally, the number of embryos per litter significantly decreased after co-housing. Compared with the model group, the low-and high-dose Res groups exhibited reduced estrous cycle disruption rates in mice, varying degrees of improvement in the number and morphology of ovarian follicles, reduced numbers of blocked ovarian follicles, improved ovarian granulosa cell apoptosis, increased ovulation, elevated ovarian wet weight and ovarian index, decreased serum FSH and LH levels, increased AMH and E_2 levels, elevated protein expression levels of YAP1 and TAZ in ovarian tissues, decreased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and increased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Furthermore, the number of embryos per litter increased to varying degrees after co-housing. In conclusion, Res effectively inhibits ovarian cell apoptosis in mice and improves ovarian responsiveness. Its mechanism may be related to the regulation of key molecules in the Hippo pathway.

Influence of propranolol plus methimazole on curative efficacy and thyroid function of patients with hyperthyroidism.

To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT). In this retrospective study, 107 cases of HT presented between August 2019 and August 2021 were grouped according to different therapeutic regimens: a control group (the Con) with 53 cases treated with MMI, and a research group (the Res) with 54 cases treated with Prop + MMI. Inter-group comparisons were performed in terms of the following domains: heart rate (HR), efficacy, adverse reactions (ARs), TF parameters (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH), hepatic function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST), and quality of life (Short-Form 36 Item Health Survey, SF-36). Finally, multivariate analysis was performed by Logistic regression to determine the risk factors leading to the ineffectiveness of treatment. The analysis showed an obviously higher total effective rate and an evidently lower AR rate in the Res compared with the Con group. Besides, the Res group had notably lower FT3, FT4, ALT and AST and statistically higher TSH after treatment compared with the baseline (before treatment) and the Con group. Higher SF-36 scores were also determined in the Res group. Finally, the results of Logistic regression analysis revealed that AST was an independent risk factor for ineffective treatment. Prop plus MMI is effective in the treatment of HT, which can effectively improve the HR, thyroid hormone levels, hepatic function, and quality of life of patients, with a lower incidence of ARs.

Dietary resveratrol improves immunity and antioxidant defense in ewes by regulating the rumen microbiome and metabolome across different reproductive stages.

Resveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation). Twenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet. Res increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation. There findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites.

Levels of serum inflammatory cytokines and their correlations with disease severity in patients with chronic spontaneous urticaria.

Inflammation is crucial in the pathogenesis of chronic spontaneous urticaria (CSU). Investigating the correlation between levels of serum inflammatory cytokines (SICs) and the severity of CSU is of great significance for understanding the disease mechanism and finding effective treatment strategies. In this context, this work was developed. This work involved a researchy group (Res group) of 114 patients with CSU and a control group (Ctrl group) of 100 healthy individuals. SICs including leukotriene B4 (LTB4), leukotriene C4 (LTC4), interleukin (IL) 4 (IL-4), IL-17, IL-31, and tumor necrosis factor-γ (TNF-γ), of patients in different groups were measured and compared. Furthermore, the correlations between each SIC and pruritus severity, duration of pruritus, urticaria activity, and quality of life (QOL) were compared among the patients in different groups. The Res group exhibited higher levels of LTB4, LTC4, IL-4, IL-17, and IL-31 but lower levels of TNF-γ. Great differences (p < 0.05) were found in IL-4, IL-17, and IL-31 among the patients with different pruritus severity, and positive correlations were observed between IL-17 and IL-31 levels and urticaria activity in the patients (p < 0.05). Additionally, levels of IL-4 and IL-31 exhibited a positive association to QOL scores in the patients, with obvious differences (p < 0.05). IL-4, IL-17, and IL-31 showed the strongest correlation with the severity of CSU, which may be attributed to their involvement in immune, inflammatory, and pruritic reactions, exacerbating the disease condition.

Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.

Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness. In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored. Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825±0.063 vs. 0.304±0.293, P=0.0141) and MAFbx (1.055±0.079 vs. 0.456±0.3, P=0.0092). Colonic tight junction proteins ZO-1 (0.550±0.087 vs. 0.842±0.094, P=0.0492) and occludin (0.284±0.057 vs. 0.664±0.191, P=0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P=0.0195) and serum of the Res group (P=0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P<0.05). Meanwhile SIRT1 protein expression were upregulated (0.320±0.035 vs. 0.685±0.081, P=0.0281) and pNF-κB protein expression were downregulated (0.815±0.295 vs. 0.258±0.130, P=0.0308). PI3K (0.365±0.142 vs. 0.763±0.013, P=0.0475), pAKT (0.493±0.159 vs. 1.183±0.344, P=0.0254) and pmTOR (0.509±0.088 vs. 1.110±0.190, P=0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels. Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.

Mechanism of protective effect of resveratrol on poor ovarian response in mice

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Effects of Aerobic vs. Resistance Exercise on Vascular Function and Vascular Endothelial Growth Factor in Older Women.

This study aimed to investigate the effects of different types of exercise (aerobic vs. resistance) on vascular function and vascular endothelial growth factor in older women. Forty-three older women, aged 65-75 years old, voluntarily participated in this study. All participants were randomly assigned to one of the following three groups: aerobic exercise (AE; n = 14), resistance exercise (RE; n = 15), and control (CG; n = 14) groups. All participants in the exercise groups performed their respective exercises for 60 min/day, three days/week, for 16 weeks. The intensity of aerobic and resistance exercises was determined using the individual heart rate reserve (40-60%) and RPE (12-13), respectively. The vascular function test included the brachial-ankle pulse wave velocity (ba-PWV), carotid artery blood flow volume, and velocity. Participants' blood samples were collected to analyze the vascular endothelial growth factor (VEGF). A significance level of 0.05 was set. Our results showed that ba-PWV improved following both AE (14.5%) and RE groups (11.1%) (all p < 0.05). Increases in carotid blood flow volume (AE: 15.4%, RE: 18.6%) and total artery peak velocity (AE: 20.4%, RE: 17%) were observed in AE and RE groups (p < 0.05), while flow total artery mean velocity (36.2%) and peak velocities (20.5%) were only increased in the aerobic exercise group (p < 0.05). VEGF was increased after resistance exercise (p < 0.05). Overall, aerobic exercise provides greater benefits on vascular function than resistance exercise but further research is needed on VEGF regarding whether this change is associated with vascular function improvement in older women.

Divergent adaptive immune responses define two types of long COVID.

The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination. Long COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29). The spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups. Multiplexed antibody analyses to 30 different viral antigens showed that LC- patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC- patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC- group. These findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID.