[Research progress on the biological effects of HIF-1α on follicle development and ovulation].

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

[Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review].

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-ß/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

MiRNA-429 alleviates ketamine-induced neurotoxicity through targeting BAG5.

Ketamine is a kind of anesthetic broadly applied in clinic. However, growing evidence has indicated that ketamine may induce neurotoxicity. Previous studies showed that mircoRNAs (miRNAs) participate in various aspects of biological regulations. In our work, we aimed to reveal the role of miR-429 in ketamine-induced neurotoxicity. The qRT-PCR was used to measure the miR-429 levels in ketamine-treated PC12 cells. TUNEL staining and caspase 3 activity detection assays were performed to assess cell apoptosis. A Cellular Reactive Oxygen Species Detection Assay Kit was utilized to detect ROS activity. A luciferase reporter assay was conducted in HEK-293T cells to test the binding between miR-429 and BAG5. Herein, we found that ketamine could induce the apoptosis and ROS activity in PC12 cells. The qRT-PCR results showed that miR-429 expression was downregulated by treatment of ketamine in a dose-dependent manner. Overexpression of miR-429 alleviated ketamine-induced neurotoxicity in PC12 cells. Mechanically, BAG5 was identified to be a target of miR-429 and negatively regulated by miR-429. Moreover, BAG5 expression was upregulated after ketamine treatment. Rescue assays revealed that overexpression of BAG5 reversed the suppressive effects of miR-429 upregulation on ketamine-induced neurotoxicity in PC12 cells. In summary, miR-429 attenuates ketamine-induced neurotoxicity in PC12 cells by the downregulation of BAG5.

Local anesthetic articaine ameliorates LPS-induced acute kidney injury via inhibition of NF-ĸB activation and the NLRP3 inflammasome pathway.

The present study was conducted to determine the protective effect of articaine (ART) in an lipopolysaccharide (LPS)-induced acute kidney injury (AKI) animal model. The results suggest ART causes a significant decrease in serum blood urea nitrogen, creatinine, and serum cystatin C level, showing a protective effect against LPS-induced AKI. This has been further supported by histopathological findings of kidney tissues. The level of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß in serum and kidney tissues was remarkably inhibited by ART in a dose-dependent manner. ART causes a significant reduction of malondialdehyde and increases the activities of glutathione and superoxide dismutase with an increase in dose as compared to the LPS-treated group. Moreover, the ART-treated group showed dose-dependent inhibition of LPS-induced nuclear factor-κB activation and TLR4 expression as confirmed by Western blot analysis. The level of Bcl-2 family genes (Bcl-2 and Bax) was restored near to normal by ART. Collectively, all the above results indicated that ART had protective effects against LPS-induced AKI by blocking inflammatory and oxidative responses.

Berberine inhibits NLRP3 Inflammasome pathway in human triple-negative breast cancer MDA-MB-231 cell.

BACKGROUND: Breast cancer is still the most common malignant tumor that threatens the female's life in the world, especially triple-negative breast cancer (TNBC), one of the most difficult subtypes. Lack of targeted therapies brings about urgent demand for novel treatments. In this study we aim to investigate the anti-tumor activity of Berberine (BBR), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 and elucidate its mechanism referring to anti-inflammation. METHODS: Cell inhibition rate was measured by Cell Proliferation Assay, the cytotoxic effects was detected by Lactate dehydrogenase (LDH) leakage assay, the colony formation and migration potential were evaluated by colony formation assay and wound healing assay, the release of inflammatory cytokines was detected by EMD multifactor detection, and alterations of proteins and genes related to the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway were analyzed using western blotting and real-time Polymerase Chain Reaction (PCR). RESULTS: BBR reduce the viability of MDA-MB-231 cells and increased the release of LDH from the cells in a dose-dependent manner, with and inhibition of colony formation potential and migration of the cells. BBR also caused a marked reduction in the secretion of proinflammatory cytokines, Interleukin-1α (IL-1α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Besides, a down-regulated behavior was observed with the expression of P2X purinoceptor 7 (P2X7), NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1 p20, Interleukin-18 (IL-18), IL-1ß proteins and NLRP3, Caspase-1 and ASC mRNAs in the NLRP3 inflammasome cascade. CONCLUSIONS: Our results confirmed that BBR can effectively affect both tumor outgrowth and spontaneous metastasis in TNBC, and that we identified a new mechanism associated with inhibition the NLRP3 inflammasome pathway, suggesting its potential therapeutic relevance in clinical use.

HDAC9 promotes brain ischemic injury by provoking IκBα/NF-κB and MAPKs signaling pathways.

Ischemic stroke is an acute cerebrovascular disease due to poor blood flow to the brain. Nevertheless, there is still no effective therapy for it and the pathology contributing to ischemic stroke is not fully understood. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme. HDAC9 gene region is a leading risk locus for large artery atherosclerotic stroke. However, the mechanisms linking HDAC9 to ischemic remain elusive. In the study, we attempted to explore HDAC9-associated inflammatory response using the wild type (WT) and HDAC9-knockout (KO) mice with brain ischemic injury. The results indicated that WT mice with ischemia brain exhibited higher expression levels of HDAC9. HDAC9 depletion resulted in a decreased infarct volume and an improved neurological function in mice after ischemic reperfusion (I/R) injury. I/R injury markedly enhanced GFAP and Iba-1 expressions in cortex and HDAC9 knockout significantly reversed this up-regulation. Loss of HDAC9 inhibited the release of inducible NO-synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and IL-18 in cortex, hippocampus and hypothalamus of mice with I/R injury, which occurred at the transcription levels. Furthermore, the inhibitory actions of HDAC9 deficiency were associated with the down-regulation of phosphorylated-IκBα, phosphorylated-nuclear factor-kappa B (NF-κB), and p-mitogen-activated protein kinases (MAPKs), including phosphorylated-p38, phosphorylated-extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated-c-Jun N-terminal kinase (JNK). Importantly, the in vitro study indicated that HDAC9 inhibition-reduced inflammation and activation of IκBα/NF-κB were restored by promoting MAPKs activity in LPS-stimulated cells. Our findings suggest that HDAC9 inhibition showed neuroprotective effects on ischemic stroke by restraining inflammation, which might help develop new and effective strategies for the therapeutic interventions in ischemic stroke.

Increase of SOX9 promotes hepatic ischemia/reperfusion (IR) injury by activating TGF-ß1.

Ischemia/reperfusion (IR) injury causes damage in aerobically metabolizing organs or tissues, which is an essential injury mechanism in various clinical settings. SRY-related high mobility group-Box gene 9 (SOX9) is a transcription factor of the SRY family, modulating various cellular processes, including fibrosis formation and tumor growth. However, the effects of SOX9 on hepatic IR injury have not been explored. In the present study, a hepatic IR injury model was established, supported by a significant histological alteration with high Suzuki scores, and a remarkable up-regulation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Importantly, we found that SOX9 was over-expressed in liver of mice after IR operation. Suppressing SOX9 markedly reduced inflammatory response, as evidenced by the reduced mRNA expressions of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1ß and inactivation of inhibitor of κBα (IκBα)/nuclear factor (NF)-κB pathway. In addition, SOX9 suppression alleviated apoptosis in liver of mice after IR injury, as supported by the reduced number of terminal deoxyribonucleotidyl transferse (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL)-staining cells and decreased expression of Caspase-3 in liver tissue sections. The role of SOX9 in accelerating hepatic IR injury was further confirmed in primary hepatocytes under hypoxiaand reoxygenation (HR) treatment by enhancing inflammatory response and apoptosis. Of note, we found that transforming growth factor (TGF)-ß1 was highly induced in liver of mice after IR injury. HR treatment also stimulated TGF-ß1 expressions in vitro. Significantly, SOX9 over-expression-induced inflammation and apoptosis were obviously reduced by pirfenidone (Pirf), TGF-ß1 inhibitor. In contrast, TGF-ß1 exposure to cells further enhanced inflammation and apoptosis in HR-operated cells either with SOX9 knockdown or over-expression. Therefore, we identified a novel SOX9-dependent pathway that contributed to hepatic IR injury through enhancing inflammation and apoptosis by activating TGF-ß1.

Suppression of Elp2 prevents renal fibrosis and inflammation induced by unilateral ureter obstruction (UUO) via inactivating Stat3-regulated TGF-ß1 and NF-κB pathways.

Renal fibrosis and inflammation are common underlying processes of progressive kidney diseases. Elongator protein 2 (Elp2), identical to signal transducer and activator of transcription-3 (STAT-3)-interacting protein-1 (Stip1), is a component of the Elongator complex that regulates RNA polymerase II. Elp2 regulates STAT-3 activation to control various cellular processes. The mechanisms of Elp2 prevention in renal interstitial fibrosis and inflammation remain unknown. In the study, Elp2 transgenic knockout (KO) and wild type (WT) mice were employed to investigate the effects of Elp2 on renal fibrosis and inflammation development after unilateral ureter obstruction (UUO) surgery. The results indicted that Elp2 was significantly expressed in renal tissues of WT/UUO mice. Elp2-KO mice exhibited attenuated histological changes of kidney, as well as collagen and fibrosis accumulation. Lower expressions of transforming growth factor (TGF)-ß1, α-smooth muscle actin (α-SMA), fibronectin, vimentin, and phospho-Smad2/3 were observed in kidney of Elp2-KO mice than that of WT mice after UUO. Elp2-KO mice showed less inflammation, as evidenced by the decrease of circulating or renal pro-inflammatory cytokines, as well as the reduction of phospho-nuclear factor (NF)-κB. Additionally, Elp2-KO apparently led to a decrease in phospho-STAT3 in kidney of UUO mice. In vitro, we found that TGF-ß1- and LPS-induced fibrosis and inflammation were abrogated by Elp2 knockdown, which were intriguingly abolished by activating STAT3 phosphorylation using its activator of colivelin (Col). Together, our findings supplied that Elp2 might be a potential therapeutic target to prevent the progression of renal fibrosis and inflammation.

HDAC11 deletion reduces fructose-induced cardiac dyslipidemia, apoptosis and inflammation by attenuating oxidative stress injury.

Diabetes mellitus (DM) is a risk factor for abnormal heart development, but the molecular mechanism remains obscure. Histone deacetylase 11 (HDAC11), the most recently identified histone deacetylase, is the sole member of class IV HDACs. However, its role in diabetic cardiac injury is still poorly understood. In the present study, we attempted to explore the effects of HDAC11 on fructose (Fru)-induced cardiac injury using the wild type (HDAC11+/+) and knockout (HDAC11-/-) mice. The results indicated that HDAC11 was significantly expressed in human and mouse diabetic heart failure (DHF) hearts. HDAC11-/- reduced the body weight, inguinal fat-pad mass, and elevated blood pressure in Fru-fed mice. Compared to HDAC11+/+/Fru group, cardiac function was significantly improved in HDAC11-/-/Fru mice. HDAC11-/-/Fru mice exhibited reduced cardiac triacylglycerol (TG), total cholesterol (TC) and free fatty acid (FFA) levels, along with decreased mRNA levels of lipid synthesis-, lipid storage- and lipid oxidation-associated genes. In addition, HDAC11-/- attenuated apoptosis, oxidative stress and inflammation in the heart of Fru-fed mice, as evidenced by the reduced cleavage of Caspase-3, nicotinamide adenine dinucleotide phosphate (NADPH), and xanthine oxidase (XOD) activity, enhanced superoxide dismutase (SOD) activity, as well as the decreased interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels, which was accompanied with down-regulated p-NF-κB. The results above were verified in Fru-treated primary cardiomyocytes isolated from HDAC11+/+ or HDAC11-/- mice. Intriguingly, suppressing the expressions of anti-oxidants using zinc protoporphyrin (ZnPP) or siNrf-2 siRNA markedly abolished the results that HDAC11 suppression-induced reduction of apoptosis, reactive oxygen species (ROS) production, inflammation, as well as the improvement of dyslipidemia in Fru-incubated primary cardiomyocytes. Thus, ROS production was responsible for HDAC11-modulated diabetic heart injury. These findings suggested that suppressing HDAC11 has therapeutic potential for treating diabetes mellitus-associated cardiac injury.

Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway.

BACKGROUND: Inflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular mechanisms by which berberine confers an anti-inflammatory effect in macrophages by upregulation of autophagy. METHODS: J774A.1 macrophages were incubated with various doses of ox-LDL for various times. We evaluated the inflammatory factors and autophagy proteins (LC3II/LC3I, and SQSTM1/p62) to ascertain the optimal dose and time. Ox-LDL-induced inflammatory factors and autophagy in J774A.1 cells were tested by the AimPlex multiplex assay, Western blotting, confocal microscopy, and transmission electron microscopy in the presence of berberine or chloroquine (CQ). Adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor compound C was used to evaluate the AMPK/mTOR signaling pathway. RESULTS: Berberine dose- and time-dependently reduced ox-LDL-induced inflammation and increased the ratio of LC3II/LC3I, and SQSTM1/p62 in J774A.1 cells. CQ significantly attenuated the berberine-induced autophagy and anti-inflammation. In addition, berberine increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR. AMPK inhibitor compound C abolished berberine-induced autophagy and promoted p-mTOR/mTOR expression in J774A.1 cells. CONCLUSION: Berberine treatment inhibits inflammation in J774A.1 cells by inducing autophagy, which is mediated through activation of the AMPK/mTOR signaling pathway. Importantly, this study provides new insight into berberine's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.

Study on therapeutic mechanism of total salvianolic acids against myocardial ischemia-reperfusion injury based on network pharmacology, molecular docking, and experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae, also known as Danshen in Chinese, effectively activates the blood and resolves stasis. Total salvianolic acids (SA) is the main active ingredient of Danshen, and related preparations, such as salvianolate injection are commonly used clinically to treat myocardial ischemia-reperfusion injury (MIRI). However, the potential targets and key active ingredients of SA have not been sufficiently investigated. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of SA in treating MIRI. MATERIALS AND METHODS: Network pharmacology and molecular docking techniques were used to predict SA targets against MIRI. The key acting pathway of SA were validated by performing experiments in a rat MIRI model. RESULTS: Twenty potential ingredients and 54 targets of SA in treating MIRI were identified. Ingredient-target-pathway network analysis revealed that salvianolic acid B and rosmarinic acid had the highest degree value. Pathway enrichment analysis showed that SA may regulate MIRI through the IL-17 signaling pathway, and this result was confirmed in the rat MIRI experiment. CONCLUSION: The results of this study indicate that SA may protect MIRI by regulating the IL-17 pathway.

Exosomes repairment for sciatic nerve injury: a cell-free therapy.

Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient's quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.

Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR-pCREB-BDNF Pathway.

BACKGROUND: Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury. MATERIALS AND METHODS: We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri's water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways. RESULTS: YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK/extracellular regulated MAP kinase, pAKT/protein kinase B, and pCREB/cAMP response element-binding were upregulated following YQTLs treatment. CONCLUSION: YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.

[Systematic evaluation of kidney-tonifying and blood-activating traditional Chinese medicines in treatment of ovulatory disorder infertility].

To evaluate clinical studies on effect of traditional Chinese medicines in treating ovulatory disorder infertility by using evidence-based medical method. According to the standard of Cochrane Handbook, the selection standard of the randomized controlled clinical trail on kidney-tonifying and blood-activating traditional Chinese medicines in the treatment of ovulatory disorder infertility was formulated. Literatures in line with the standard were searched through computers among Chinese and English databases. The literatures included were evaluated by evidence-based medicine method, and analyzed with Revman 5. 1. There were 19 articles in line with the standard. Data for pregnancy rate, ovulation rate and miscarriage rate was extracted from them, and heterogeneity test was conducted with Meta, which showed no statistical heterogeneity. Results showed pregnancy rate (n = 17) , RRp 1. 66, 95% C1 [1. 45, 1.92], Z7.06 (P<0.000 01); ovulation rate (n =11) , RRo 1.05, 95% CI[0.97,1. 12], Z 1.25 (P=0.21); miscarriage rate (n =5) , RRM, 0. 24, 95% CI[0. 11,0. 56] , Z 3.33 (P =0. 000 9). After analysis and comparison, it is found that the Chinese medical treatment group was superior to the Western medicine control group in terms of pregnancy rate, which showed statistic significance. Both groups showed no obvious difference in the ovulation rate, and no statistic significance; the miscarriage rate of the Chinese medicine group is obviously lower than that of the Western medicine control group, which indicated statistic significances. This study preliminarily proves the good efficacy and unique advantages of kidney-tonifying and blood-activating traditional Chinese medicines in treating ovulatory disorder infertility.

[Observation on clinical efficacy of activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility].

OBJECTIVE: To discuss the clinical efficacy of the activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility. METHOD: Eighty-six cases were randomly divided into two groups: the treatment group and the control group. The treatment group is administered with the activating renal blood circulation and ovarian stimulation formula (composed of 15 g Cuscutae Semen, 15 g Dipsaci Asperoidis Radix, 15 g Lycii Fructus, 15 g Spatholobi Caulis, 10 g Ligustri Lucidi Fructus, 15 g Lycopi Herba, 10 g Typhae Polleu, 10 g Angelicae Sinensis Radix, 15 g Cyathulae Radix etc.), whereas the control group was given clomiphene. RESULT: The treatment group showed a pregnancy rate of 58.14%, with an ovulation rate of 68.6%. While the control group showed a pregnancy rate of 36.67%, with an ovulation rate of 70%. CONCLUSION: The comparison between the two groups showed that the activating renal blood circulation and ovarian stimulation formula was significantly different from clomiphene in statistical analysis (P < 0.05), without notable difference in the ovulation rate. Before and after the treatment, there is no significant difference in diameter of dominant follicles between the two groups, with remarkable difference in endometrium (P < 0.05).

Protective effects of baicalin against L-glutamate-induced oxidative damage in HT-22 cells by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.

Objectives: To explore the ability and underlying molecular mechanisms involved in the protective effects of Baicalin (BA) against L-Glutamate-induced mouse hippocampal neuron cell line HT-22. Materials and Methods: The cell injury model of HT-22 cells was induced by L-glutamate, and cell viability and damage were detected by CCK-8 and LDH assays. Generation of intracellular reactive oxygen species (ROS) was measured by DCFH-DA in situ fluorescence method. The SOD activity and MDA concentration in the supernatants were determined by WST-8 and colorimetric method, respectively. Furthermore, Western blot and real-time qPCR analysis were utilized to detect the expression levels of the Nrf2/HO-1 signaling pathway and NLRP3 inflammasome proteins and genes. Results: L-Glutamate exposure induced cell injuries in HT-22 cells, and the concentration of 5 mM L-Glutamate was chosen to be the modeling condition. Co-treatment with BA significantly promoted cell viability and reduced LDH release in a dose-dependent manner. In addition, BA attenuated the L-Glutamate-induced injuries by decreasing the ROS production and MDA concentration, while increasing the SOD activity. Moreover, we also found that BA treatment up-regulated the gene and protein expression of Nrf2 and HO-1, and then inhibited the expression of NLRP3. Conclusion: Our study found that BA could relieve oxidative stress damage of HT-22 cells induced by L-Glutamate, and the mechanism might be related to the activation of Nrf2/HO-1 and inhibition of NLRP3 inflammasome.

Efficacy and underlying mechanisms of berberine against lipid metabolic diseases: a review.

Lipid-lowering therapy is an important tool for the treatment of lipid metabolic diseases, which are increasing in prevalence. However, the failure of conventional lipid-lowering drugs to achieve the desired efficacy in some patients, and the side-effects of these drug regimens, highlight the urgent need for novel lipid-lowering drugs. The liver and intestine are important in the production and removal of endogenous and exogenous lipids, respectively, and have an important impact on circulating lipid levels. Elevated circulating lipids predisposes an individual to lipid deposition in the vascular wall, affecting vascular function. Berberine (BBR) modulates liver lipid production and clearance by regulating cellular targets such as cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC), microsomal triglyceride transfer protein (MTTP), scavenger receptor class B type 1 (SR-BI), low-density lipoprotein receptor (LDLR), and ATP-binding cassette transporter A1 (ABCA1). It influences intestinal lipid synthesis and metabolism by modulating gut microbiota composition and metabolism. Finally, BBR maintains vascular function by targeting proteins such as endothelial nitric oxide synthase (eNOS) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). This paper elucidates and summarizes the pharmacological mechanisms of berberine in lipid metabolic diseases from a multi-organ (liver, intestine, and vascular system) and multi-target perspective.

The glymphatic system: a new perspective on brain diseases.

The glymphatic system is a brain-wide perivascular pathway driven by aquaporin-4 on the endfeet of astrocytes, which can deliver nutrients and active substances to the brain parenchyma through periarterial cerebrospinal fluid (CSF) influx pathway and remove metabolic wastes through perivenous clearance routes. This paper summarizes the composition, overall fluid flow, solute transport, related diseases, affecting factors, and preclinical research methods of the glymphatic system. In doing so, we aim to provide direction and reference for more relevant researchers in the future.

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

Introduction: Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective. Methods: We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model. Results: Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant. Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

[Clinical analysis of 106 cases on effect of supplementing qi and nourishing yin recipe in treating anovulatory dysfunctional uterine bleeding].

OBJECTIVE: To observe the clinical treatment of supplementing qi and nourishing yin recipe and progestogen. METHOD: One group was treated using traditional Chinese medicine decoction, which was made of Danshen, Shenghuangqi, Wuweizi, Baishao, Nvzhenzi, Hanliancao and Wuzeigu, and the other group was medroxyprogesterone acetate (depogeston). RESULT: After 3 menstrual cycles of treatment, the recovery rate of the treatment group was 43.42%, with 27.63% of marked effectiveness,18.42% of positive effects, and 10.53% of inefficiency. The total effective rate was 89.47%. The recovery rate of the control group was 23%, with 47% of marked effectiveness, 20% of positive effects, and 10% of inefficiency. The total effective rate was 90.00%. With statistically comparison, there was no obvious difference. The treatment group was higher than the control group on the Chinese symptom, the two groups were significantly different (P < 0.05). The treatment group and the control group was no obvious difference on Hb, PLT, PT, APTT. The treatment group and the control group was no obvious difference on FSH, LH, E2, P. CONCLUSION: Traditional Chinese medicine decoction should be recommended for its better therapeutic efficacy and stable clinical effects such as high recovery rate, significant improvement of symptom and no side effect and no adverse reaction.