Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB 1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD = 1.34, 95% CI [0.96,1.72]) and AMH levels (MD = 1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD = 0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis].

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Wheat Germ-Derived Peptide Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice.

This study explores the protective properties and potential mechanisms of wheat-germ-derived peptide APEPEPAF (APE) against ulcerative colitis. Colitis mice induced by dextran sulfate sodium (DSS) were used as the animal model. The results showed that the APE peptide could alleviate colitis symptoms including weight loss, colon shortening, and histopathological changes. This peptide attenuated the generation of inflammatory cytokines by inhibiting the phosphorylation of protein kinase PKCζ (Thr410) and NF-κB transcriptional activity in DSS-induced mice, suggesting that APE ameliorates colitis inflammation by regulating the PKCζ/NF-κB signaling pathway. APE also preserved the barrier function of the colon by dose-dependently promoting the expression of tight junction proteins (claudin-1, zonula occluded-1, and occludin). In addition, APE significantly decreased the abundance of Bacteroides and increased the abundance of Dubosiella and Lachnospiraceae_UCG-006 to improve the intestinal flora imbalance in DSS-induced colitis mice. Therefore, wheat germ peptide APE can be used as a novel agent and dietary supplement to treat ulcerative colitis..

Rapid Profiling of Metabolites Combined with Network Pharmacology to Explore the Potential Mechanism of Sanguisorba officinalis L. against Thrombocytopenia.

Sanguisorba officinalis L. (SO), a well-known herbal medicine, has been proven to show effect against thrombocytopenia. However, metabolites of SO in vivo are still unclear, and the underlying mechanism of SO against thrombocytopenia from the aspect of metabolites have not been well elucidated. In this study, an improved analytical method combined with UHPLC-QTOF MS and a molecular network was developed for the rapid characterization of metabolites in vivo based on fragmentation patterns. Then, network pharmacology (NP) was used to elucidate the potential mechanism of SO against thrombocytopenia. As a result, a total of 1678 exogenous metabolites were detected in urine, feces, plasma, and bone marrow, in which 104 metabolites were tentatively characterized. These characterized metabolites that originated from plasma, urine, and feces were then imported to the NP analysis. The results showed that the metabolites from plasma, urine, and feces could be responsible for the pharmacological activity against thrombocytopenia by regulating the PI3K-Akt, MAPK, JAK-STAT, VEGF, chemokine, actin cytoskeleton, HIF-1, and pluripotency of stem cells. This study provides a rapid method for metabolite characterization and a new perspective of underlying mechanism study from the aspect of active metabolites in vivo.

"Click" preparation of a chiral macrocycle-based stationary phase for both normal-phase and reversed-phase high performance liquid chromatography enantioseparation.

Chiral polyimine macrocycles (CPMs) constitute a new family of organic macrocycles that have defined cavities, rigid shapes, inherent chirality and multiple cooperative binding sites, and have shown great potential in diverse areas. However, the application of CPMs for high performance liquid chromatography (HPLC) enantioseparation has rarely been reported. In this work, a novel chiral stationary phase (CSP) for HPLC was prepared by chemical bonding of a CPM (C54H72N6O3) onto thiolated silica via thiol-ene click reaction. The CSP exhibited good enantioselectivity in both normal- and reversed-phase HPLC. Chiral compounds included alcohols, diols, ketones, organic acids, esters, ethers, amines, and epoxides were enantioseparated on the column in normal-phase mode (17 compounds) and reversed-phase mode (20 compounds). Importantly, broader chiral resolution was observed with the column than that obtained using our previously studied chiral macrocycle H3L-based column, indicating the potential to significantly improve and broaden applicability of this novel macrocycle-type CSPs. Moreover, the CSP exhibited good complementary enantioseparation to Chiralpak AD-H and Chiralcel OD-H columns, enabling separation of some racemates that could not be separated by the two popular chiral HPLC columns. In addition, the fabricated column exhibited good stability and reproducibility. The relative standard deviations (RSDs) (n = 5) of retention time and resolution after multiple injections were < 0.20 % and < 0.39 %, respectively. The results demonstrated the great potential of this type of CPM for HPLC separation of enantiomers.

A peptide from wheat germ abolishes the senile osteoporosis by regulating OPG/RANKL/RANK/TRAF6 signaling pathway.

BACKGROUND: Oxidative stress played a key role in the development of bone brittleness and is an important pathogenic factor of senile osteoporosis. A variety of animal and plant-derived peptides have been shown to have significant anti-osteoporosis effects in vivo and in vitro. PURPOSE: In this study, we aim to explore the possible mechanism of wheat germ peptide ADWGGPLPH on senile osteoporosis. STUDY DESIGN: Naturally, aged rats were used as animal models of senile osteoporosis. METHODS: Wheat germ peptide ADWGGPLPH was administered from 9-months-old to 21-months-old, and the effect of ADWGGPLPH on preventing senile osteoporosis was evaluated by measuring serum biochemical indexes, bone histomorphometry, bone biomechanics, and other indexes to elucidate the mechanism of ADWGGPLPH in delaying senile osteoporosis by detecting the expression of osteoporosis-related proteins. RESULTS: The results showed that ADWGGPLPH could effectively reduce the level of oxidative stress and improve the microstructure and bone mineral density in senile osteoporosis rats. In addition, ADWGGPLPH could improve the proliferation and differentiation activity of osteoblasts and effectively inhibit osteoclasts' differentiation by regulating the OPG/RANKL/RANK/TRAF6 pathway. CONCLUSION: ADWGGPLPH from wheat germ exhibited a notably effect on senile osteoporosis and has a high potential in the development of the nutrient regimen to against senile osteoporosis.

Chemical characterization and DPP-IV inhibitory activity evaluation of tripeptides from Gynura divaricata (L.) DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura divaricata (L.) DC. (GD), a herbal medicine, has been used for the prevention and treatment of hyperglycemia in China. However, hypoglycemic ingredients within GD have not yet been well studied. AIM OF THE STUDY: The aim of this study was to explore undiscovered compounds with dipeptidyl peptidase IV (DPP-IV) inhibitory activity within GD. MATERIALS AND METHODS: A four-step strategy was developed to explore undiscovered DPP-IV inhibitors within GD. First, the components were preliminarily characterized using UHPLC-HRMS combined with a library search. Second, preliminarily characterized compounds were searched for potential bioactivity. Third, a mixture of these preliminarily characterized compounds was isolated and thoroughly characterized based on fragmentation patterns associated with molecular networking. Fourth, the activities of these compounds were verified using DPP-IV inhibitory assay and molecular docking. RESULTS: Diprotin A, a tripeptide inhibitor against DPP-IV, was identified. Thereafter, a mixture of twenty-five diprotin A analogs was isolated and characterized, which exhibited IC50 of 0.40 mg/mL for DPP-IV. Molecular docking results also confirmed the interactions between the tripeptide analogs and DPP-IV mainly via H-bonds and hydrophobic interactions. CONCLUSIONS: This is the first report of DPP-IV inhibitors within GD. These findings demonstrate that the extract of GD might be beneficial for the treatment of type 2 diabetes mellitus, and is expected to promote further development and utilization of GD in herbal medicine.

In vitro anti-motile effects of Rhoifolin, a flavonoid extracted from Callicarpa nudiflora on breast cancer cells via downregulating Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition.

BACKGROUND: Callicarpa nudiflora (C. nudiflora), which is a medical herb in genus of Callicarpa, widely grows in the southern part of China. Several investigations had shown that this herb exerts anti-tumor effects. Ezrin is an important membrane-cytoskeleton-binding protein. By organizing membrane proteins and orchestrating their signal transduction, Ezrin contributes to modulation of cytoskeleton rearrangement in cell motility. PURPOSE: To investigate the anti-motile properties of Rhoifolin (RFL), a flavonoid from C. nudiflora, and to determine whether its effects are related to the inhibition on Podocalyxin (PODXL)-Ezrin signal transduction. METHODS: To determine suitable concentration of RFL and exposure time on breast cancer cells, the effects of RFL on viability of breast cancer cells were evaluated by MTT assay. Then, the anti-migratory properties of RFL were determined by AP 48 chamber system and ORISTM cell migration assay. F-actin in MDA-MB-231 cells was visualized by Alexa Fluor™ 488 conjugated Phalloidin. Immunoprecipitation was involved to access the effects of RFL on the interaction between Ezrin and PODXL. In addition, several EMT markers, including E-cadherin, Vimentin, Snail and Slug, were measured by Western Blotting assay and cell immunofluorescent analysis. Finally, the effects of RFL on cell migration, expression of Ezrin and EMT markers were verified by small interfering RNA (siRNA) mediated gene silencing. RESULTS: We showed here that treatments with 10 and 40 µM of RFL induced significant inhibitions on cell migration and alterations on the location and organization of actin cytoskeleton in breast cancer cells. Next, it was found that RFL suppressed Ezrin phosphorylation and consequent interaction with PODXL, significantly. Also, this compound showed an obvious inhibitory effect on TGF-ß1-induced EMT in MDA-MB-231 cells. Furthermore, data from RNA interfering assay confirmed that the inhibitory effects of RFL on Ezrin was enhanced by the deletion of Ezrin. CONCLUSION: RFL shows anti-motile properties on breast cancer cells, which is due to its potential to downregulate Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition.

Less is more: Silver-AIE core@shell nanoparticles for multimodality cancer imaging and synergistic therapy.

Nanomaterials with integrated multiple imaging and therapeutic modalities possess great potentials in accurate cancer diagnostics and enhanced therapeutic efficacy. Traditional strategies for achieving multimodality nanoplatform through one by one combination of different modalities are challenged by the complicated structural design and fabrication as well as inherent incompatibility between different modalities. Herein, a novel strategy is presented to realize multimodal imaging and synergistic therapy using a class of simple silver core/AIE (aggregation-induced emission) shell nanoparticles. In addition to the intrinsic AIE fluorescence (FL) and metal-based computed tomography (CT) and radiation therapy (RT) properties, an extra functionality at the core/shell interface was identified to enable excellent photothermal (PT) and photoacoustic (PA) performance. As a result, five imaging and therapy modalities (FL, CT, PA, photothermal therapy (PTT), and RT) were achieved with a single structural unit for sensitive tumor imaging and effective therapy.

Updated progress in susceptibility genes and environmental response genes of Kaschin-Beck disease / 中华地方病学杂志

Kaschin-Beck disease is an endemic and deformed chronic osteochondropathy. Though the etiology is not well clear, the etiologic hypotheses have been mainly focused on bio-geochemical hypotheses, the hypotheses of mycotoxin poisoning under low selenium condition and the hypotheses of toxic organic compounds in drinking water. Prevention and control measures based on these hypotheses have shown remarkable achievements. Depending on the related research at home and abroad, this paper reviews the new developments of pathogen, pathogenesis and prevention on Kaschin-Beck disease in recent years.In terms of scientific research,new progresses have been made in the aspects of environmental factors associated with the pathogenesis of Kaschin-Beck disease, molecular biology, genomics, proteomics and environmental response genes. As for prevention and treatment, new progress has been made in such fields as supplement of selenium and treatment of traditional Chinese medicine.

[Entecavir combined with Fufang Biejia Ruangan tablet in treatment of chronic hepatitis B patients with liver fibrosis: 96-week efficacy analyses].

OBJECTIVE: To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis. METHODS: A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging. RESULTS: Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate. CONCLUSION: The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.

[Effect of Yifei Jianpi Recipe on Airway Inflammation and Airway Mucus Hypersecretion of Chronic Obstructive Pulmonary Disease Model Rats].

OBJECTIVE: To observe preventive and therapeutic effect of Yifei Jianpi Recipe (YJR) on chronic obstructive pulmonary disease (COPD) model rats and to explore its mechanism from the way of airway inflammation and airway mucus hypersecretion. METHODS: The COPD rat model was established by using cigarette smoking combined with intratracheal injection of lipopolysaccharide (LPS). Male SD rats were randomly divided into the blank control group (control group), the model group, the YJR group, 6 in each group. Forced vital capacity (FVC), forced expiratory volume in 0. 1 second (FEV0. 1), FEVO. 1/FVC, peak expiratory flow (PEF) was tested by lung function device. Pathological changes of bronchi and lung tissues were observed by HE staining. Airway Goblet cells were observed using AB-PAS staining. Contents of IL-8, IL-17, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Protein expressions of intercellular cell adhesion molecule-1 (ICAM-1), nuclear factor KB (NF-KB), mucin 5AC (Muc5AC), and Toll-like receptor 4 (TLR4) in rat airway were detected by immunohistochemical assay. mRNA expressions of TLR4 and Muc5AC in bronchi and lung tissues were detected by real-time quantitative PCR (RT qPCR). RESULTS: Changes of bronchi and lung tissues in the model group rats were consistent with typical pathological manifestations of COPD. Compared with the model group, the degree of lung injury was significantly alleviated in the YJR group. Compared with the control group, FVC, FEV0. 1, FEVO. I/FVC, and PEF were decreased (P <0. 01), contents of IL-8, IL-17, and TNF-α in BALF were significantly increased (P <0. 01), protein expressions of ICAM-1, NF-KB, Muc5AC, and TLR4, mRNA expression levels of Muc5AC and TLR4 in bronchi and lung tissues were also significantly increased in the model group (P <0. 01). Compared with the model group, FVC, FEV0. 1, FEV0. 1/FVC, and PEF were significantly increased in the YJR group (P <0. 01, P <0. 05), but the rest indices were significantly lowered (P <0. 01, P <0. 05). CONCLUSION: YJR could decrease contents of IL-8, IL-17, and TNF-α in BALF of COPD model rats, inhibit protein expression levels of ICAM-1, NF-κB, Muc5AC, and TLR4.in airway and lung tissues, thus playing preventive and therapeutic roles by reducing airway inflammation and airway mucus hypersecretion.

Uniform fluorescent nanobioprobes for pathogen detection.

Manipulating biochemical reactions in living cells to synthesize nanomaterials is an attractive strategy to realize their synthesis that cannot take place in nature. Yeast cells have been skillfully utilized to produce desired nanoparticles through spatiotemporal coupling of intracellular nonrelated biochemical reaction pathways for formation of fluorescent CdSe quantum dots. Here, we have successfully transformed Staphylococcus aureus cells into cellular beacons (fluorescing cells), all of which are highly fluorescent and photostable with perfect uniformity. Importantly, on the basis of such cells, we efficiently fabricated fluorescent nanobioprobes by a specific interaction between the protein A expressed on the S. aureus surface and the Fc fragment domain of antibodies, avoiding the use of other common methods for cell surface modifications, such as molecular covalent connection or more difficult genetic and metabolic engineering. Coupled with immunomagnetic beads, the resulting fluorescent-biotargeting bifunctional cells, i.e., biotargeting cellular beacons, can be employed as nanobioprobes for detection of viruses, bacteria, and tumor cells. With this method, H9N2 AIV can be detected specifically with a limit of 8.94 ng/mL (based on protein content). Furthermore, diverse probes for detection of different pathogens or for other biomedical applications can be easily obtained by simply changing the antibody conjugated to the cell surface.

[Effect of catgut implantation at acupoint on the content of tumor necrosis factor alpha of patients with ankylosing spondylitis].

OBJECTIVE: To observe the effect of catgut implantation at acupoint on the content of tumor necrosis factor alpha (TNF-alpha), and to explore its mechanism for treatment of ankylosing spondylitis (AS). METHODS: Seventy-four AS patients were randomly assigned to the observation group and the control group by digit random table, 37 in each group. Patients in the control group took Sulfasalazine Enteric-coated Tablet (SECT), 0.5 g each time, three times daily for 3 months. Those in the observation group additionally received catgut implantation at acupoint for 3 months. Changes of visual analogue scale (VAS), Schober test, pillow wall distance, thoracic activity, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and TNF-alpha were compared after 3 months of treatment. RESULTS: There was obvious change in VAS, Schober test, pillow wall distance, thoracic activity, ESR, CRP, and TNF-alpha after treatment in the both groups, showing statistical difference when compared with before treatment (P < 0.05, P < 0.01). The aforesaid indices were obviously improved after treatment in the observation group (P < 0.05, P < 0.01). CONCLUSION: Catgut implantation at acupoint, as an assistant therapy, could significantly improve clinical symptoms and signs, decrease the level of TNF-alpha, and its effect was superior to that of oral SECT administration alone.