Serum ALP Research Articles

Effects of Vitamin D Supplementation and a Cafeteria Diet on Various Parameters in the Next Generation of Rats with Metabolic Syndrome

Background/Objectives: Metabolic Syndrome (MetS) is an increasingly widespread public health problem worldwide. MetS is associated with a cafeteria diet characterized by high fat and high simple carbohydrates. A cafeteria diet significantly affects serum glucose, creatine, urea, triglyceride, cholesterol and MetS parameters such as ALT, AST and ALP. Due to its epigenetic effects, vitamin D is important in controlling MetS parameters and minimizing MetS findings in subsequent generations. Methods: In this study, the effect of weekly 0.3 mL (1.000 IU/week) vitamin D intervention on MetS parameters was investigated in parental rats developing high-fructose MetS and their offspring. Offspring of MetS rats receiving and not receiving vitamin D supplementation were divided into four different groups and exposed to a cafeteria diet and vitamin D supplementation for eight weeks. Results: It was shown that parental rats in the intervention group had lower serum urea, glucose, creatine, total cholesterol, ALP, AST and ALT levels (p < 0.05). Serum urea, glucose, creatine, ALT, AST, ALP, triglyceride, total cholesterol levels and body weights were lower and HDL levels were higher in the offspring (p < 0.05). However, initial serum ALT and AST values were higher in the offspring of MetS parent rats receiving vitamin D supplementation and in the offspring of rats not receiving supplementation than in the offspring of supplemented parents. Conclusions: In conclusion, it was found that vitamin D supplementation improved MetS parameters in parent rats, positively affected MetS parameters in offspring rats despite an inadequate diet, and positively affected some MetS parameters by affecting epigenetic pathways in offspring born to MetS mothers.

Health risk assessment of toxic metals and DNA damage in somatic and germ cells by soil and groundwater of a major cement factory in Nigeria.

The waste generated from cement manufacturing is an important source of heavy metal contamination of groundwater and soil. This study investigated the concentration of toxic metals in the soil of a major cement factory and nearby groundwater. Ecological and carcinogenic risks of the metals were calculated. Potential reproductive toxicity and genotoxic effects of the samples were assessed in sex and somatic cells of male mice using sperm abnormalities and bone marrow micronucleus (MN) assays, respectively. Also, the serum ALP, ALT, AST, Total Testosterone (TT), Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH); and liver SOD and CAT activities were measured in the treated mice. Cr, Cu, Ni, Zn, Mn, Cd, and Pb levels in the soil and groundwater exceeded the allowable maximum standard. Ingestion and dermal contact were the most probable routes of human exposure with children having about three times higher probability of exposure to the metals than the adults. Ni, Pb, and Cr presented carcinogenic risks in children and adults. In the MN result, nuclear abnormalities in the studied mice especially micronucleated polychromatic erythrocytes increased significantly (p < 0.05). Compared to the negative control, the ratio of PCE/NCE showed the cytotoxicity of the two samples. Data further showed a significant increase in the serum ALP, AST, and ALT while the liver CAT and SOD activities concomitantly decreased in the exposed mice. Sperm morphology result showed that the samples contained constituents capable of inducing reproductive toxicity in exposed organisms, with alterations to the concentrations of TT, LH, and FSH. Toxic metal constituents of the samples were believed to induce these reported reproductive toxicity and genotoxic effect. These results showed the environmental pollution caused by cement factory and the potential effects the pollutants might have on exposed eukaryotic organisms.

The association of glyphosate exposure with kidney stones in American adults: A nationally representative cross-sectional study

ObjectiveGlyphosate has been ubiquitously present in our living environment due to its efficient herbicidal ability, but its association with the prevalence of kidney stones remains uncertain. This study aims to explore the impact of glyphosate exposure on kidney stones and to investigate the mediating effects of some serologic indicators. Furthermore, we attempt to identify the specific populations at greater risk of exposure. MethodsThis is a cross-sectional study of the U.S. adult population examining the association between glyphosate exposure and kidney stones based on data from the 2013–2018 National Health and Nutrition Examination Survey (NHANES). We implemented multi-model-adjusted logistic regression and smoothed curve fitting to explore the connection between them. Further subgroup analyses were conducted to confirm the magnitude of exposure risk in specific populations. Mediation effects analysis served to provide insight into the underlying mechanisms of the link. ResultsA total of 4302 participants' health data were ultimately analyzed, and the prevalence of kidney stones was 10.85 %. Participants with the highest urinary glyphosate(uGLY) content(Q3) had a higher prevalence of kidney stones compared with participants with the lowest uGLY content(Q1) (OR=1.70, 95 %CI: 1.10–2.63). Smoothed curve fitting revealed a linear positive association between ln-transformed uGLY and kidney stones (OR=1.21,95 %CI:1.08–1.37, LLR=0.291), and this exposure-outcome effect was at greater risk in men (OR=1.24,95 %CI: 1.05–1.46), non-Hispanic whites (OR=1.29, 95 %CI: 1.09–1.53), and hypertensive groups (OR=1.23,95 %CI: 1.05–1.44). Serum biochemical markers HDL, ALP, and serum glucose partially mediated the correlation between glyphosate and kidney stones (2.44–4.20 %). ConclusionGlyphosate exposure is significantly associated with the prevalence of kidney stones. In men, non-Hispanic whites, and hypertensive populations, the management of glyphosate exposure should be emphasized, and appropriate protective strategies may be beneficial in reducing the burden of kidney stones. More high-quality clinical inquiries and animal toxicology experiments are still required to verify the reliability of our findings and their underlying mechanisms.

Vitamin U alleviates AFB1-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B1 (AFB1) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB1 group (AF, 0.3 mg AFB1/kg b.w.), the Vitamin U group (U, 50 mg Vitamin U/kg b.w.), the AFB1 + Vitamin U group (AU, 50 mg Vitamin U /kg b.w. + 0.3 mg AFB1/kg b.w.), the control group (DMSO), and the MOCK group (distilled water). They were administered substances by gavage every day for 28 days. Results indicated that exposure to AFB1 increased the liver index and caused histological disruptions. Elevated serum levels of ALT and ALP were observed, along with a significant increase in liver MDA content and a decrease in GSH-Px and T-SOD levels. Moreover, the Keap1 and Hmox1 gene was downregulated with statistical significance, while the IL1β and TNFα gene were significantly upregulated. Vitamin U was demonstrated by the organized structure of liver cells in tissue slices, effectively reducing liver cell necrosis. This intervention was associated with a significant decrease in serum ALT and ALP activities, as well as a significant decrease in liver MDA content. Additionally, there were significant increases in liver T-SOD and GSH-Px levels, along with upregulation of mRNA and protein expression of Nfr2, Hmox1 and Keap1, and downregulation of mRNA expression of the IL1β gene. In summary, Vitamin U mitigated oxidative stress-induced liver injury by modulating the Nrf2/Hmox1 signaling pathway and inflammatory factors affected by AFB1.

Protective effects of Khaya senegalensis stem bark extracts against acetaminophen-induced oxidative damage, dyslipidaemia, and hepatotoxicity in rats

Background Free radical attacks have been implicated in the aetiology of many diseases and several plants are used traditionally for the management of many oxidative-stress related diseases. Khaya senegalensis is used traditionally for the management diseases such as diabetes and for the treatment of infections. However, mechanisms underlying actions of K. senegalensis are poorly understood. Purpose This study aimed at the preliminary determination of the phytochemical constituents and investigation of the antioxidative and hepatoprotective actions of K. senegalensis in acetaminophen-treated rats. Method Aqueous extracts of K. senegalensis were screened for the presence of key phytochemicals. Total flavonoid and phenolic contents were quantified. Wistar albino rats were pre-treated with saline (control) or graded concentrations of K. senegalensis (50 – 200mg/kgbw) for 10 days prior to acetaminophen (2g/kg body weight) administration. Serum levels of vitamin C, thiobarbituric reactive substances, catalase activities, enzyme markers of liver function were assessed. Cholesterol-phospholipid ratio in treated-rats were determined. Results K. senegalensis extract showed the presence of saponins, tannins, cardiac glycosides, alkaloids, flavonoids and phenolic compounds. Total phenolic and total flavonoid contents were determined as 57.14±0.85mgQE/g and 51.72±0.77mgGE/g. Acetaminophen (2g/kg bw) raised serum TBARS (4.7-fold, P&lt;0.001), H2O2 levels (2.3-fold, P&lt;0.001), AST (5.9-fold, P&lt;0.001), ALT (6.6-fold, P&lt;0.001) and ALP (4.2-fold, P&lt;0.001) and reduced serum levels of vitamin C (54%, P&lt;0.001) and catalase activity (74.6%, P&lt;0.001). Treatment of K. senegalensis extracts inhibited effects of acetaminophen on TBARS (18.2% - 46.4%, P&lt;0.05 – 0.001), vitamin C (1.4 – 1.8-fold, P&lt;0.001 – 0.05), H2O2 levels (19.1 – 50.1%, P&lt;0.001-0.05), catalase activities (1.4 – 3.1-fold, P&lt;0.001 – 0.05), AST (27.7 – 62.8%, P&lt;0.001 – 0.05), ALT (35.6 – 57.5%, P&lt;0.001 – 0.05) and ALP (15.9 – 46.2%, P&lt;0.01 – 0.05). The extract reduced cholesterol-phospholipid ratio (21 – 31%, P&lt;0.05). Conclusion These results motivate further development of the therapeutic potential of K. senegalensis

Desmodium styracifolium (Osb.) Merr. Extracts alleviate cholestatic liver disease by FXR pathway

Ethnopharmacological relevanceCholestatic liver disease (CLD) is a disease characterized by cholestasis. Farnesoid X receptor (FXR) is a nuclear receptor that maintains homeostasis in bile acid metabolism. Studies have shown that gut microbiota interfered with the FXR pathway. Modulation of FXR to inhibit cholestasis has become a key measure in the treatment of CLD. In traditional folk medicine, Desmodium styracifolium (Osb.) Merr. was used as a primary treatment for gallstones, gonorrhea, jaundice, cholecystitis and other diseases. Modern pharmacological studies had also found that the herb has anti-calculus, anti-inflammatory, antioxidant, diuretic and liver damage. Therefore, we speculated that Desmodium styracifolium (Osb.) Merr. extracts (DME) could alleviate CLD through the FXR pathway and might be associated with the gut microbiota. However, studies of DME alleviating CLD through the FXR pathway have not been reported. Aim of studyTo study the effect and mechanism of DME in relieving CLD through in vivo and in vitro experiments. Materials and methodsFirst, mice were administrated with alpha-naphthyl isothiocyanate (ANIT) to establish a CLD model in vivo. Meanwhile, HepG2 cells were induced by lithocholic acid (LCA) to establish the CLD model in vitro. To evaluate the therapeutic effect of DME on CLD mice, hematoxylin-eosin (HE) staining, and biochemical indicators were performed. The prototype of the blood components in mice serum was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 16S rDNA sequencing was used to analyze the gut microbiota. Finally, the protein and mRNA expression of the FXR pathway in mice liver tissues or HepG2 cells were detected by Western blot, qRT-PCR, or immunofluorescence. ResultsPathological testing and biochemical indexes showed that DME significantly reduced serum ALT, AST, ALP, TBIL, DBIL, TBA and liver TBA levels, and attenuated liver tissue injury, necrosis and jaundice in CLD mice. In addition, MetagenomeSeq analysis of gut microbiota showed that DME significantly up-regulated the abundance of Parvibacter, down-regulated the abundance of Paenalcaligenes, and regulated bile acid homeostasis. In terms of mRNA expression, DME significantly upregulated the mRNA levels of Nr1h4, Abcb11, Cyp7a1 and Slc10a1. Meanwhile, in terms of protein expression, DME significantly up-regulated the protein expression levels of FXR, BSEP, CYP7A1 and NTCP, which regulated bile acid homeostasis. Finally, the molecular docking results showed that the components of DME, such as Lumichrome, Daidzein and Folic acid, all had good binding ability with FXR, and the surface plasmon resonance (SPR) results also showed that both Lumichrome and Daidzein had a relatively high affinity with FXR. ConclusionDME alleviated CLD through the FXR pathway, and the mechanisms might be associated with the gut microbiota.

Propensity score matching-based analysis of the effect of corticosteroids in treating severe drug-induced liver injury

Background and aimThere is no conventional treatment for patients with severe drug-induced liver injury (DILI) except for discontinuation of liver injury drugs and symptomatic supportive therapy. Opinions on whether corticosteroids can be used to treat severe DILI are conflicting, and most of the relevant clinical studies are case reports or retrospective studies, which still need to be supported by high-level evidence-based medical studies. This study aimed to evaluate the effect and tolerance of corticosteroids in patients with severe DILI. Risk factors associated with patient failure to cure were also explored. MethodsPropensity score matching based on nearest-neighbor 1:1 matching was used to screen severe DILI patients in the corticosteroids and control groups. Severe DILI was defined as elevated serum ALT and/or ALP with TBIL≥5 ULN (5 mg/dL or 85.5 μmol/L) with or without INR ≥1.5. Patients were treated with conventional therapy combined with corticosteroids in the corticosteroids group and only conventional therapy in the control group. ResultsA total of 146 patients, 73 each in the corticosteroids and control groups, were included in this study. By analyzing the entire cohort, we found no significant difference in cure rates between patients in the corticosteroid group and control group (34.2% vs. 20.5 %, p = 0.095), and there was no significant difference in the incidence of adverse effects between the two groups (20.5% vs. 20.5 %, p = 1.000). However, TBIL decreased more in the corticosteroids group on day 7 (89.2 ± 107.6 μmol/L vs. 58.8 ± 70.7 μmol/L, p = 0.046). In subgroup analyses, patients whose TBIL remained elevated despite conventional treatment had a higher TBIL decline on day 7,14 after use of corticosteroid (99.2 ± 98.5μmol/L vs. -23.3 ± 50.4μmol/L, p < 0.001; 120 ± 119.1μmol/L vs. 61.2 ± 98.5μmol/L, p = 0.047). The cure rate of patients in the corticosteroid group was significantly higher than that of the control group (36.1 % versus 4.5 %, p = 0.016). The proportion of patients with TBIL <85.5 μmol/L was also significantly higher in the corticosteroid group than in the control group at day 7 (p = 0.016) and day 14 (p = 0.004) after treatment. In the subgroup analysis of patients with different clinical phenotypes, the causative agent was herbal, autoimmune antibody-positive and 40 % < PTA ≤ 50 % of patients, corticosteroid use did not increase the cure rate of the patients. Univariate and multifactorial analyses found corticosteroid use to be a protective factor for failure to cure in patients with severe DILI (p < 0.001, OR:0.191,95 % CI:0.072–0.470), and peak TBIL to be a risk factor (p = 0.003, OR:1.016,95 % CI:1.007–1.028). ConclusionsThe addition of corticosteroids could not increase the cure rate in patients with severe DILI, but it could rapidly reduce the patient's TBIL at an earlier stage. Corticosteroids could also promote curing in patients with elevated TBIL after conventional treatment. Corticosteroid use was a protective factor for failure to cure in patients with severe DILI and peak TBIL was a risk factor.

Polyherbal Formulation Development, Evaluation and Pharmacological Screening for Hepatoprotective Activity.

The current research work investigates the hepatoprotective action of polyherbal formulation prepared from ethanolic extracts of Azadirachta indica A. Juss, Moringa oleifera Lam, Cymbopogon citrates (DC.) Stapf, Tinospora cordifolia (Thumb.) Miers, Ricinus communis L., against experimental hepatotoxicity. The World Health Organization (WHO) is promoting herbal remedies derived from traditional medicinal plants in several countries. The main goal of this investigation was to create and evaluate the polyherbal formulation to protect albino Wistar rats against the hepatotoxic effects of CCl4. Three potential suspensions, polyherbal formulations A, B, and C, were formulated by trituration method using ethanolic extracts of specific medicinal plant components with different sodium carboxy methyl cellulose concentrations 1, 1.5, and 2%, respectively and evaluated the same for both certain physiochemical parameters, including organoleptic characteristics, pH, viscosity, sedimentation volume, redispersibility, density, specific gravity, zeta potential, and accelerated stability studies for three months and for hepatoprotective activity also. Evaluation parameters for Polyherbal Formulation-C have shown good results that met the specifications, with pleasant texture and appearance. Along with other physiochemical qualities, like pH, viscosity, flow rate and sedimentation, were all unchanged and showed significant hepatoprotective effects by reducing elevated serum enzyme levels SGOT, SGPT, ALP, total and direct bilirubin. It was discovered that each quality control parameter in the polyherbal suspension C formulation was thoroughly adequate and improved the recovery from hepatotoxicity caused by CCl4. These findings suggest that the produced polyherbal suspension C (containing ethanolic extracts of A. indica A. Juss, M. oleifera Lam, C. citrates (DC.) Stapf, T. cordifolia (Thumb.) Miers, R. communis L. may be stable, secure, and effective for use and exhibited notable hepatoprotective effects, possibly resulting from the combined impact of all these extracts.

Mitigation of methylglyoxal-induced hepatotoxicity by Boerhavia diffusa L. aerial extract: Insights from cellular and animal models

BackgroundBoerhavia diffusa (Punarnava), is a perennial herb with a long-standing reputation for its antioxidative and anti-inflammatory properties, dating back to ancient times. Methylglyoxal is an advanced glycation end-product, known to be toxic in liver cell line as well as in mice model. Our objective is to illustrate the protective action of punarnava aerial extracts in methylglyoxal-induced hepatotoxicity in cell line and mice model. MethodsPunarnava aerial parts were collected and different solvent extracts were prepared in methanol, dichloromethane and hexane by maceration followed by their LCMS/MS characterization, determination of total phenolic, total flavonoid contents and antioxidant activity by DPPH reagent. Cell viability of the extracts and methylglyoxal was assessed using different cell lines. In vitro protective effect of punarnava methanolic extract (PME) against methylglyoxal was evaluated by cell migration assay, NO and ROS production assays and Oil Red O staining in HepG2 cell line. BALB/c mice were pretreated with Punarnava methanolic extract (200 mg/kg and 400 mg/kg) for seven days followed by 290 mg/kg methylglyoxal administration for 6 hrs to induce hepatotoxicity. Serum glucose, AST, ALT, ALP and GSH level were checked and liver histopathological damages were identified. ResultsAmong the three Punarnava extracts, PME possessed maximum antioxidant, total phenolic and flavonoid content as well as least cytotoxic to liver cell line. Methylglyoxal showed maximum toxicity in HepG2 cells with IC50 (50 % inhibitory concentration) 3 µM. PME confers protection against methylglyoxal-induced cytotoxicity by decreasing ROS, promoting cell migration and preventing loss of cell viability. No significant change was observed in NO production and Oil Red O staining. PME-treated mice showed decrease in liver ALP levels and glucose with intact cellular morphology compared to hepatocyte steatosis and nuclear degeneration in methylglyoxal-treated group. DiscussionsIndigenous herb Punarnava is effective in protecting liver cells from damage induced by the glycolytic byproduct, methylglyoxal.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

Evaluation of Anti-arthritic Activity of hydro-alcoholic Root Extract of Moringa concanensis in complete Freund’s Adjuvant-induced Arthritic Rats

Background: Arthritis, a debilitating inflammatory disorder, has been a target for numerous therapeutic interventions. Natural plant extracts, especially those rich in phytochemicals like terpenoids, have demonstrated potential as alternative remedies. In this context, Moringa concanensis, a traditionally known medicinal plant, needs further elucidation regarding its anti-arthritic efficacy. Objective: This study aimed to investigate the anti-arthritic potential of the hydro-alcoholic root extract of Moringa concanensis in a Complete Freund’s Adjuvant (CFA)-induced arthritis rat model. Methods: An initial phytochemical screening and GC-MS analysis were executed on the hydro-alcoholic root extract of Moringa concanensis. Arthritis was subsequently induced in rats using CFA. Comprehensive assessments were made on various parameters such as body weight, paw volume, joint diameter, serum rheumatoid factor, serum C-reactive protein, ALP, ALT, total protein, total cholesterol, and urea. Additionally, histopathological studies of the liver and ankle joints were carried out. For comparative efficacy, methotrexate was employed as a positive control. Results: Rats receiving the hydro-alcoholic extract at dosages of 200mg/kg (p.o) and 400mg/kg (p.o) exhibited a notable reduction in the physical and biochemical indicators of arthritis, in comparison to the untreated arthritic model. Histopathological observations further confirmed that the anti-arthritic effects of the hydro-alcoholic extract were on par with methotrexate. Conclusion: The hydro-alcoholic root extract of Moringa concanensis exhibited significant anti-arthritic activity, possibly attributed to its terpenoid content. The findings advocate for its potential application as a therapeutic agent in managing arthritis.

Evaluation of Hormonal and Biochemical Profile of Ladakhi Cow during Estrous Cycle: The Future Perspective of Reproductive Management of Ladakhi Cow

The Ladakhi cow is an indigenous breed from Ladakh, India, and has a unique genetic makeup to adapt to high-altitude hypobaric stress. Furthermore, little study is available on examining the Ladakhi cow’s blood biochemicals and reproductive hormonal status during various stages of the estrus cycle. Hence, the current study was conducted on eight reproductively mature Ladakhi cows at the experimental dairy cattle unit in Leh-Ladakh, India, to determine the changes in serum biochemical and hormonal levels during the estrus cycle. The estrus behaviour was initially observed before the blood sampling on days 0 (the day the cow exhibited heat symptoms), 2nd, 8th, 17th, and 21st days. The serum was isolated for biochemical and hormonal profiling as per standard procedures using commercially available kits. The results revealed that serum biochemicals, viz. Ca, Fe, ALT, AST, ALP, TG, TP, Albumin, Glucose, UA, Creatinine, and Urea levels were within the normal range of cows at high altitudes. However, reproductive hormones, e.g. GnRH, FSH, LH, progesterone, estrogen, PGF2α, IGF-1, and Insulin varied from the reference level at different stages of the estrus cycle. This study’s findings have provided new insights into the serum biochemical and hormonal profiling of Ladakhi cows during the estrus cycle and this information may help to develop a reference range and baseline value for the serum biochemicals and hormonal levels of Ladakhi cows for other breeding programs and health monitoring.

Down-regulation of miR-29 improves lipid metabolism in fatty liver of dairy cows

In this study, we conducted a thorough investigation into the mechanisms by which miR-29 influences lipid metabolism. Thirty-two cows were selected and categorized into distinct groups based on their liver triglyceride (TG) content: healthy, mild fatty liver, and moderate fatty liver groups. Dairy cows with moderate fatty liver showed higher levels of hepatic lipid accumulation, MDA content and serum AST, ALT and ALP contents and lower hepatic catalase CAT and SOD activities. Subsequently, hepatocytes isolated from healthy calves were exposed to sodium oleate (SO) in the presence or absence of pre-incubation with miR-29 inhibitor or inhibitor NC. Pre-transfection with miR-29 inhibitor resulted in reduced hepatocyte lipid accumulation and MDA levels, as well as decreased levels of AST, ALT, and ALP in the supernatant. In the miR-29 inhibitor + SO group, there was an increase in the expression of SREBP-1, FAS, SCD1, and Sirt1. Meanwhile, the expression of PPARα, CPT1, CPT2, PGC-1α, NRF-1, UCP2, and miR-29 were observed to be decreased. In comparison to the miR-29 inhibitor + SO group, some of the measured indicators showed partial reversal in the miR-29 inhibitor + siSirt1 + SO group. Collectively, these findings provide evidence that miR-29 may play a crucial role in the pathogenesis of fatty liver in dairy cows.

Long-Term Oral Administration of Hyperimmune Egg-Based IgY-Rich Formulations Induces Mucosal Immune Response and Systemic Increases of Cytokines Involved in Th2- and Th17-Type Immune Responses in C57BL/6 Mice.

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

The regulatory effects of water probiotic supplementation on the blood physiology, reproductive performance, and its related genes in Red Tilapia (Oreochromis niloticus X O. mossambicus)

Probiotics are becoming increasingly popular as eco-friendly alternatives in aquaculture. However, there is limited research on their impacts on the reproductive efficiency of Red Tilapia (Oreochromis niloticus x O. mossambicus) broodstock. Therefore, this experiment aimed to explore the combined effects of selective probiotics Bacillus subtilis and B. licheniformis (BSL; 1:1) added to water on blood hematology, serum metabolites, gonadal histology, reproductive performance, and reproductive associated genes in Red Tilapia broodstock. Tilapia broodfish weighing 140–160 g were stocked in four treatment groups: control (T0), and the other three groups were added different levels of BSL to the water as follows: T1 (0.01 g/m3), T2 (0.02 g/m3), and T3 (0.03 g/m3), respectively. Results indicate that BSL administration significantly improved RBCs, hemoglobin, hematocrit, MCH, and MCHC, with the highest improvement seen in the T3 group (P < 0.05). BSL added to the fish water significantly enhanced serum protein fractions (total protein, albumin, and globulins), while AST, ALT, ALP, creatinine, uric acid, and glucose were significantly diminished in a dose-dependent way (P < 0.05). Adding 0.02–0.03 g/ m3 of BSL resulted in higher antioxidant status (superoxide dismutase and catalase) compared to other groups (P < 0.05). Testosterone levels were higher in T3 than in other groups (P < 0.05). All female hormones (LH, FSH, estradiol, and progesterone) were substantially augmented by the addition of BSL. Additionally, the BSL groups exhibited higher GSI, HSI, VSI (male only), egg diameter (mm), mean number of fry/fish, and mean fry weight (g) compared to the control group (P < 0.05). Expression of reproductive-associated genes (vasa, nanos1a, nanos2, dnd1, pum1, AMH, and vtg) were significantly up-regulated in the gonads of fish in the 0.03 g/m3 treatment. The histological gonadal structure exhibited that BSL improved gonad maturation in both genders of Tilapia fish. Overall, adding a mixture of B. subtilis and B. licheniformis (0.03 g/m3 water) can accelerate reproductive performance in Red Tilapia through up-regulation of reproductive genes and enhance the health profile.

The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC

ABSTRACT The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA–induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA–induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats.

The present study evaluated the anti-arthritic impact of combined crocin and curcumin on Adjuvant Induced Arthritis (AIA) in rats. The arthritis model was induced in rats by injecting Complete Freund's adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti- arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats. The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlβ and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg, respectively), as well as MTX, revealed a suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti- arthritic effects owing to their anti-inflammatory effects. Crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis.

Comparison of the Efficacy and Safety of 12 Chinese Patent Medicines for Treating Primary Osteoporosis Patients: A Systematic Review and Network Meta-Analysis

Objective: To elucidate the effectiveness and safety of different traditional Chinese medicines (TCMs) for treating primary osteoporosis (POP) using network meta-analysis. Materials and Methods: We conducted a systematic review and network meta-analysis to assess the efficacy and safety of Chinese patent medicine (CPM) combined with conventional Western medicine for POP treatment. From March 5, 2004, to March 5, 2024, electronic databases such as the Cochrane Library, VIP, PubMed, Embase, CBM, Wanfang, CNKI, and Web of Science were comprehensively searched. Only randomized controlled trials (RCTs) were included in this systematic review. After screening and data extraction, the Cochrane risk of bias evaluation tool was utilized to assess the methodological quality of the included studies. Stata 15.1 was utilized to synthesize the data. Results: In total, 44 studies involving 4859 patients were included. There were 2577 patients in the treatment group and 2282 in the control group, with 12 types of CPMs. Qing'e Pill, in combination with conventional treatment, significantly improved the total effective rate [relative risk (RR) = 2.57, 95% confidence interval (CI) (1.32, 5.00)]. In combination with conventional treatment, Liuwei Dihuang Pill significantly increased the bone mass density (BMD) of the lumbar spine [WMD = 0.17, 95% CI (0.05, 0.28)] and femoral neck [WMD = 0.23, 95% CI (0.11, 0.35)]. Furthermore, Hugu capsules effectively decreased the VAS score [WMD = −2.48, 95% CI (−3.85, −1.11)]. The presence of the genus Gusongbao markedly decreased the serum ALP concentration [WMD = −15.67, 95% CI (−32.73, 1.39)]. In all studies, no serious adverse reactions were noted, with most studies suggesting only mild gastrointestinal reactions. Conclusions: CPM and conventional treatment combo enhances POP therapy; each CPM offers unique benefits. More high-quality RCTs needed for conclusions. Meds tailored to patient traits in clinics.

Analysis of occurrences and causes of abnormal liver function in 109 patients with COVID-19.

COVID-19 is a novel coronavirus pneumonia, which is related to abnormal liver function. Thus, it is important to explore the occurrences and causes of abnormal liver function with COVID-19. We chose 109 patients with COVID-19 in 2020 and studied the relationship between gender, age, basic diseases, antiviral drug treatment, disease classification, and abnormal liver function, and analyzed the causes of abnormal liver function in patients with COVID-19. Among patients, 46 (42.20%) had abnormal liver function at admission; 37 (80.43%) had mild abnormal liver function; and 9 (19.57%) had severe liver function. Compared with other age groups, the abnormal rate of serum ALP in the group younger than 21 years old were the highest (P < 0.05). The abnormal rates and concentrations of serum ALT, AST and γ-GT in the male groups were higher than in female groups (P < 0.05), basic disease group were higher than those in the non-basic disease group (P < 0.05). Serum γ-GT concentration after 1 week of antiviral treatment was higher than that before treatment (P < 0.05). The abnormal rate of ALT and AST at discharge was lower than that after antiviral treatment for 1 week (P < 0.05). Serum TB and AST concentrations at discharge were lower than those before treatment (P < 0.05). Serum AST and γ-GT concentrations in severe/critical type group were higher than those in mild or ordinary type group (P < 0.05). In this study, we found male sex, basic diseases, antiviral drugs, and severe/critical types are related to the occurrence of abnormal liver function in COVID-19 patients.

Based on NF-κB and Notch1/Hes1 Signaling Pathways, the Mechanism of Artesunate on Inflammation in Osteoporosis in Ovariectomized Rats was Investigated.

Artesunate (ART) has the potential to modulate the nuclear factor kappa B (NF-κB) and Notch1/Hes1 signaling pathways, which play crucial roles in the pathogenesis of osteoporosis. This study aims to explore whether ART participates in the progression of osteoporosis by regulating these signaling pathways. In the in vitro experiments, we treated bone marrow mesenchymal stem cells (BMSCs) with different concentrations of ART (0, 3, 6, 12 µM) and evaluated osteogenic differentiation using alkaline phosphatase staining (ALP) and alizarin red S staining (ARS) staining. The expression levels of osteocalcin (OCN), RUNT-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), and receptor activator of the nuclear factor kappa ligand (RANKL) were detected by real-time quantitative PCR (RT-qPCR). The effects of ART on NF-κB p65 and Notch1 protein expression were analyzed by Western blot (WB) and immunofluorescence (IF). In the in vivo experiments, a postmenopausal osteoporosis rat model was established via ovariectomy. Bone tissue pathological injury was evaluated using hematoxylin eosin (HE) staining. Serum ALP levels were measured using a kit, bone density was determined by dual-energy X-ray absorptiometry, and serum levels of bone gla protein (BGP), OPG, RANKL, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of NF-κB p65 and Notch1 in tissues was assessed by immunohistochemistry. In vitro experiments revealed that compared to the control group, ART dose-dependently promoted BMSCs proliferation and enhanced their osteogenic differentiation capability. The expression of OCN, RUNX2, and OPG significantly increased in the ART-treated group, while RANKL expression decreased significantly (p < 0.05). ART significantly inhibited the expression of NF-κB p65 and Notch1/Hes1 signaling pathway proteins (p < 0.05). Compared to ART treatment alone, combined treatment with ART and phorbol myristate acetate (PMA) or valproic acid (VPA) resulted in increased expression of NF-κB p65 and Notch1 proteins and decreased osteogenic differentiation capability (p < 0.05). In vivo experiments showed that in rats treated with ART, bone damage was significantly reduced, bone density and mineral content were restored considerably, and the expression of inflammatory factors (TNF-α, IL-6, IL-1β) decreased significantly (p < 0.05). Additionally, ART treatment significantly reduced the expression of NF-κB p65 and Notch1 proteins, increased OPG expression, and decreased BGP and RANKL levels (p < 0.05). In summary, ART facilitates the osteogenic differentiation of BMSCs by inhibiting the NF-κB and Notch1/Hes1 signaling pathways, thereby exerting significant protective effects against osteoporosis.