OBJECTIVE: To explore the therapeutic effect of polygonum cuspidatum glycoside on steroid-induced osteonecrosis of the femoral head(SONFH) in rats and its potential mechanism of protecting bone tissue by regulating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway(JAK2/STAT3). METHODS: Fifty male SD rats were randomly divided into control group, model group, low-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-L), high-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-H), and polygonum cuspidatum glycoside-H+Colivelin (JAK2/STAT3 pathway activator) group. SONFH model was induced by lipopolysaccharide and dexamethasone. The treatment groups were given polygonum cuspidatum glycoside orally(polygonum cuspidatum glycoside-L 10 mg·kg^-1, polygonum cuspidatum glycoside-H 20 mg·kg^-1, and the polygonum cuspidatum glycoside-H+Colivelin group was injected with Colivelin (1 mg·kg^-1) intraperitoneally once a day, while the control and model groups were given an equal volume of saline for 6 weeks. The observed indicators included serum calcium(Ca), serum phosphorus (P), alkaline phosphatase, and transforming growth factor β1(TGF-β1) levels, micro-CT scanning, hematoxylin-eosin staining, and Western blot detection of JAK2/STAT3 signaling pathway and osteogenic differentiation marker genes, including Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), and osteopontin (OPN) protein expression. RESULTS: Compared with the model group, the trabecular bone area percentage in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups was significantly increased, and the empty lacunar rate was significantly decreased (P<0.05). Micro-CT analysis showed that the bone volume fraction, trabecular number, and thickness increased, and the trabecular separation decreased in the polygonum cuspidatum glycoside-treated groups(P<0.05). Serum biochemical tests found that the serum Ca and P concentrations in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups were restored, the alkaline phosphatase levels decreased, and the transforming growth factor β1 levels increased (P<0.05). Western blot analysis showed that polygonum cuspidatum glycoside significantly inhibited the activation of the JAK2/STAT3 signaling pathway in the model group and promoted the expression of osteogenic differentiation marker genes such as Runx2, BMP2, and OPN (P<0.05). Compared with the polygonum cuspidatum glycoside-H group, the improvements in the polygonum cuspidatum glycoside-H+Colivelin group were somewhat weakened, indicating the importance of the JAK2/STAT3 signaling pathway in the action of polygonum cuspidatum glycoside. CONCLUSION polygonum cuspidatum glycoside promotes osteogenic differentiation, improves bone microstructure, and has significant therapeutic effects on rat SONFH by regulating the JAK2/STAT3 signaling pathway.
Animals ; Male ; Janus Kinase 2/physiology* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Glucosides/pharmacology* ; STAT3 Transcription Factor/genetics* ; Femur Head Necrosis/chemically induced* ; Stilbenes/pharmacology*

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

OBJECTIVE: To evaluate the protective effects of resveratrol against acute lung injury (ALI) and investigate the potential mechanisms underlying the reactive oxygen species (ROS)-triggered thioredoxin-interacting protein (TXNIP)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway. METHODS: C57BL/6 mice and J774A.1 cells were selected as the research subjects. Thirty Mice were randomly divided into 5 groups of 6 in each group: control with 0.9% saline, 5 mg/kg lipopolysaccharide (LPS) 24 h, 25 mg/kg resveratrol + 5 mg/kg LPS, 100 mg/kg resveratrol + 5 mg/kg LPS, and 4 mg/kg NLRP3 inhibitor CY-09 + 5 mg/kg LPS. For cell stimulation, cells were pretreated with 5 and 20 µmol/L resveratrol for 2 h, and stimulated with or without 1 µg/mL LPS and 3 mmol/L ATP for 2 h. The antioxidant N-acetyl-L-cysteine (NAC, 2 µmol/L) was used as the positive control group. Hematoxylin and eosin staining was used to evaluate the degree of lung LPS-induced tissue damage, and enzyme-linked immunosorbent assay was used to evaluate the contents of interleukin-1 β (IL-1 β) and IL-18 in the serum and cell supernatant. ROS and malondialdehyde (MDA) levels in the lung tissue were detected using the corresponding kits. Western blotting was used to detect the expressions of TXNIP, high-mobility group box 1 (HMGB1), NLRP3, as well as cysteine-aspartic acid protease 1 (caspase-1) and gasdermin D (GSDMD) along with their cleaved forms in lung tissue. Additionally, reverse transcription quantitative polymerase chain reaction was performed to analyze the expression of related inflammatory cytokines. ROS content was detected using flow cytometry and confocal laser microscopy. Mitochondrial morphological changes were observed using transmission electron microscopy, and HMGB1 expression was detected using immunofluorescence. RESULTS: Resveratrol significantly alleviated LPS-induced lung damage with reduced inflammation, interstitial edema, and leukocyte infiltration (P<0.01). It also decreased serum levels of IL-1 β and IL-18 (P<0.05), while downregulating the expressions of NLRP3, IL-6, and other inflammatory markers at both the protein and mRNA levels (P<0.05). Notably, the higher dose (100 mg/kg) demonstrated a better effect than the lower dose (25 mg/kg). In macrophages, resveratrol reduced IL-1 β and IL-18 following LPS and ATP stimulation, suppressed HMGB1 translocation, and inhibited formation and activation of the NLRP3 inflammasome (P<0.05 or P<0.01). These anti-inflammatory effects were mediated through the suppression ROS accumulation (P<0.01) and mitochondrial dysfunction. Transmission electron microscopy revealed that resveratrol preserved mitochondrial structure, preventing the mitochondrial damage seen in LPS-treated groups (P<0.01). The expressions of cleaved caspase-1, cleaved GSDMD, and cytoplasmic HMGB1 were all reduced following resveratrol treatment (P<0.01). Moreover, resveratrol inhibited dissociation of TXNIP from thioredoxin, blocking subsequent activation of NLRP3 and downstream inflammatory cytokines (P<0.01). Similarly, the higher concentration of resveratrol (20 µ mol/L) exhibited superior efficacy in vitro. CONCLUSION Resveratrol can reduce the inflammatory response following ALI and inhibit the activation of NLRP3 inflammasome and the level of HMGB1 in the cytoplasm by inhibiting ROS overproduction.
Acute Lung Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Resveratrol/pharmacology* ; Reactive Oxygen Species/metabolism* ; Inflammation/complications* ; Mice, Inbred C57BL ; Carrier Proteins/metabolism* ; Signal Transduction/drug effects* ; Lipopolysaccharides ; Thioredoxins/metabolism* ; Mice ; Lung/drug effects* ; Male ; Cell Line ; Interleukin-1beta/metabolism* ; Cell Cycle Proteins ; Stilbenes/therapeutic use*

Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGT_BS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.
Stilbenes/chemistry* ; Glucosides/biosynthesis* ; Resveratrol ; Fallopia japonica/chemistry* ; Glycosyltransferases/genetics*

This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na ⁺-K ⁺-ATPase and Ca ²⁺-Mg ²⁺-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Animals ; Resveratrol ; Male ; Liver/pathology* ; Rats, Sprague-Dawley ; Rats ; Hindlimb Suspension ; Oxidative Stress/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Stilbenes/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis/drug effects*

Humans ; Dermatitis, Atopic/drug therapy* ; Resorcinols/therapeutic use* ; Stilbenes/therapeutic use* ; Double-Blind Method ; Treatment Outcome ; Severity of Illness Index

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
Female ; Humans ; Anastrozole ; Aromatase Inhibitors/therapeutic use* ; Bilirubin ; Breast Neoplasms/drug therapy* ; Letrozole ; Liver ; Retrospective Studies ; Toremifene ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.
Tamoxifen/therapeutic use* ; Selective Estrogen Receptor Modulators/therapeutic use* ; Cognition ; Nervous System

OBJECTIVES: To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. METHODS: After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. RESULTS: After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 μmol/L. After treatment with 1 800 μmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G₀/G₁ and S phases, with a significantly increased proportion of cells in the G₀/G₁ phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). CONCLUSIONS Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Glucosides/pharmacology* ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Signal Transduction ; Stilbenes/pharmacology* ; THP-1 Cells ; TOR Serine-Threonine Kinases

Objective: To investigate the protective effect of diallyl sulfide (DAS) , against benzene-induced genetic damage in rat. Methods: In September 2018, Sixty adult male adaptive feeding 5 days, were randomly divided into six groups according to their weight. Control groups, DAS control groups, benzene model groups, benzene+low DAS groups, benzene+middle DAS groups, benzene+High DAS group, 10 in each group. Rats in the DAS and DAS control group were orally given DAS at 40, 80, 160, 160 mg/kg, blank control and benzene model groups were given corn oil in the same volume. 2 h later, the rats in the benzene model and DAS treatment groups were given gavage administration of benzene (1.3 g/kg) mixed with corn oil (50%, V/V) , blank and DAS control groups were given corn oil in the same volume. Once a day, for 4 weeks. Samples were collected for subsequent testing. Results: Compared with the blank control group, In benzene treated rat, peripheral WBC count was reduced 65.06% (P=0.003) , lymphocyte ratiowas reduced (P=0.000) , micronucleus rate was increased (P=0.000) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in BMCs were increased 32.69%、32.64% (P=0.001、0.008) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in PBLs were increased 397.70%、396.26% (P=0.000、P=0.003) respectively. Compared with the benzene model group, the WBC count increased respectively (P=0.000、0.003、0.006) and the micronucleus rate decreased (P=0.000、0.000、0.000) in the DAS groups, Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in BMCs were significantly reduced in the high DAS groups (P=0.000、0.000) , Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in PBLs were significantly reduced in the low, middle, high DAS groups (P=0.000、0.000) . Conclusion: DAS can effectively suppress benzene induced genotoxic damage in rats.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid/analogs & derivatives* ; Allyl Compounds/pharmacology* ; Animals ; Benzene/toxicity* ; Corn Oil ; DNA Damage ; Male ; Rats ; Sulfides/pharmacology*