Tea consumption and risk of bone health: an updated systematic review and meta-analysis.

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.

Dissecting the efficacy of the use of acupuncture and Chinese herbal medicine for the treatment of premature ovarian insufficiency (POI): A systematic review and metaanalysis.

Premature ovarian insufficiency is a multi-factor gynecological disease that has become a major global health problem. In recent years, several trials have explored the treatment of premature ovarian insufficiency using Chinese herbal medicine and acupuncture, but the efficacy and safety of this combination remains controversial. This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of combining Chinese herbal medicine with acupuncture to treat premature ovarian insufficiency. From eight different databases, we retrieved randomized controlled trials wherein Chinese herbal medicine and acupuncture had been compared with western medicine in the treatment of premature ovarian insufficiency. The bias risk assessment stipulated by the Cochrane Collaboration's tool was utilized to evaluate the quality of the chosen randomized controlled trials. This meta-analysis was executed with the help of Review Manager 5.3 and Stata 10.0. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A total of 10 randomized controlled trials involving 594 premature ovarian insufficiency patients were included in the analysis. Compared with western medicine, co-treatment with acupuncture and Chinese herbal medicine exhibited a significantly higher total effective rate (relative risk: 1.21; 95% confidence interval: 1.12-1.31; P < 0.01, I2 = 0%), but lower levels of luteinizing hormone (standardized mean difference: -0.57; 95% confidence interval: -1.06, -0.08; P < 0.05, I2 = 80%), follicle-stimulating hormone, and Kupperman index score. Moreover, the combined intervention increased estradiol level in the serum. Overall, the data demonstrate that acupuncture plus Chinese herbal medicine is an efficacious and safe treatment option for POI patients. These findings must be verified by conducting large-scale, multicenter, high-quality, and long-term randomized controlled trials.

Coffee, Green Tea Intake, and the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies.

Several studies suggest an inverse relationship between coffee intake and risk of hepatocellular carcinoma (HCC), but the association between green tea intake and the risk of HCC is still inconclusive. We performed a meta-analysis of observational studies to clarify the association. We identified eligible studies published from January 1, 1992, to February 28, 2022, by searching PubMed, Web of Science, and EMBASE. A total of 32 studies were included in the meta-analysis. Among them, 21 studies involving 2,492,625 participants and 5980 cases of HCC reported coffee intake, 18 studies involving 1,481,647 participants and 6985 cases of HCC reported green tea intake, and seven studies reported both coffee intake and green tea intake. The results showed that a higher coffee (RR = 0.53; 95% CI: 0.47-0.59; I2 = 0.0%; Pheterogeneity = 0.634) or green tea (RR = 0.80; 95% CI: 0.67-0.95; I2 = 72.30%; Pheterogeneity < 0.001) intake may be associated with a lower risk of HCC. The same results were observed in both cohort and case-control subgroups. Our findings suggest that drinking coffee or green tea may be a potentially effective approach for the prevention or mitigation of HCC, but this still needs to be confirmed by further well-designed observational studies and clinical experimental research.

Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra-performance liquid chromatography-tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts.

The herb pair Epimedii Folium-Chuanxiong Rhizoma (EF-CR), derived from the classical traditional Chinese medicine 'Xian Ling Pi San', has a distinctive compatibility therapeutic profile and is clinically safe and effective. This study aimed to investigate and compare the pharmacokinetic characteristics of nine analytes in osteoarthritis (OA) rat plasma after the oral administration of EF, CR or a combination of these two herbs. We developed an ultra-performance liquid chromatography method coupled with quadrupole linear ion-trap mass spectrometry to simultaneously quantify and assess the pharmacokinetics of icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ferulic acid, ligustilide and senkyunolide A of the EF-CR pair in the plasma of osteoarthritic rats. The pharmacokinetic parameters showed that the absorption of multiple components was significantly enhanced and residence time was prolonged in the EF-CR group (P < 0.05) compared to the single-herb group. These parameters revealed that the combination of EF and CR exhibited synergistic effects of the nine bioactive components, suggesting the potential application of the EF-CR combination for the treatment of OA.

Adaptation of Melodic Intonation Therapy to a Tone Language: A Pilot Study of Tone-Rhythmic Therapy in Mandarin Chinese.

INTRODUCTION: Although melodic intonation therapy (MIT) has proven effective in individuals with non-fluent aphasia in a variety of western languages, its application to Mandarin-speaking aphasic patients has not been thoroughly studied. The adaptation is complicated because Mandarin Chinese is a tone language with specific prosodic elements that differ from Indo-European languages. This study developed a Chinese-specific variant of MIT, i.e., tone-rhythmic therapy (TRT), and tested its efficacy in individuals with non-fluent aphasia. METHODS: Six non-fluent aphasic patients were recruited; all of them were admitted to the study over 6 months after stroke and had received a standard program of language therapy. In the current research, tone and rhythmic practice were incorporated into the training procedures, and the adaptation was then examined in patients. The TRT treatment lasted 6 weeks, with five 50-min sessions per week. The Boston Diagnostic Aphasia Examination (BDAE) and the Functional Assessment of Communication Skills for Adults (FACS) tests were used to measure the change in the speech and language skills of patients. RESULTS: The results showed that the patients had increased BDAE and FACS scores after intervention, and the treatment effect lasted for 6 months. DISCUSSION: The modified MIT proved effective for Mandarin-speaking patients with non-fluent aphasia with lasting effects. Further studies evaluating its efficacy are needed for other types of aphasia and other tone languages.

Microbial community succession in the fermentation of Qingzhuan tea at various temperatures and their correlations with the quality formation.

With the aim to reveal the microbial community succession at various temperatures in the fermentation of Qingzhuan tea (QZT), the Illumina NovaSeq sequencing was carried out to analyze bacterial and fungal community structure in tea samples collected from the fermentation set at various temperatures, i.e., 25 °C, 30 °C, 37 °C, 45 °C, 55 °C, and room temperature. The results showed that fermentation temperature profoundly affected the microbial community succession in the QZT fermentation. Microbial richness and community diversity decreased along with the increase of fermentation temperature. Despite the differences between microorganisms and their metabolic types among various temperatures, most bacteria and fungi showed positive correlations at the genera level. Klebsiella, Paenibacillus, Cohnella, and Pantoea were confirmed as the main bacterial genera, and Aspergillus and Cyberlindnera were the main fungal genera in QZT fermentation. The microbial genera (i.e. Aspergillus, Rhizomucor, Thermomyces, Ralstonia, Castellaniella, and Vibrio) were positively correlated with fermentation temperature (P < 0.05), while Klebsiella, Paenibacillus, and Aspergillus had good adaptability at different temperatures. Conversely, Pantoea and Cyberlindnera were only suitable for low temperature (≤37 °C) growth, and Thermomyces was only suitable for high temperature (>37 °C) growth. Aspergillus had a significant positive correlation with tea aroma quality (r = 0.64, p < 0.05). This study would help to understand the formation mechanism of QZT from microflora perspective.

Bu-Shen-Ning-Xin decoction alleviates premature ovarian insufficiency (POI) by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway.

PURPOSE: To explore the therapeutic effects of Bu-Shen-Ning-Xin decoction (BSNXD) on POI and the underlying mechanism. METHODS: VCD was used to induce the in vivo and in vitro POI model. HE staining was used to evaluate the pathological state of ovarian tissues. ELISA was used to detect the production of hormones in the serum and granule cells (GCs). An immunohistochemical assay was used to determine the expression of ATG7 and p-AKT in the ovarian tissues. The number of oocytes in POI rats was counted. The mitochondrial membrane potential (MMP) in oocytes and GCs was detected by flow cytometry. A Western blot assay was used to measure the expression of AKT, p-AKT, p-mTOR, mTOR, S6K, p-S6K, ULK1, p-ULK1, Beclin-1, Bcl-2, LC3-II, LC3-I, ATG7, and cleaved Caspase3. The numbers of autophagosomes were detected by transmission electron microscope and autophagic flux assay. The CCK-8 assay was used to detect the cell viability. RESULTS: Decreased primary follicles in the ovarian tissues, elevated concentration of FSH, and LH, suppressed concentration of E2 and AMH in the serum, reduced number of oocytes, and mitochondrial dysfunction in oocytes induced by VCD were significantly reversed by BSNXD. Activated autophagy state and inhibited PI3K/AKT/mTOR pathway stimulated by VCD in both ovarian tissues and GCs were dramatically reversed by BSNXD. The protective effect of BSNXD on VCD-treated GCs was abolished by LY294002, an inhibitor of the PI3K/AKT/mTOR pathway. CONCLUSION: Our data revealed that BSNXD alleviated POI by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway.

Influence of thermophilic microorganism on non-volatile metabolites during high-temperature pile-fermentation of Chinese dark tea based on metabolomic analysis.

Pile-fermentation is a critical procedure for producing Chinese dark tea, during which thermophilic microorganisms would play an irreplaceable role. However, there have been little researches on the influences of thermophilic microorganism pile-fermentation (TMPF) in high-temperature of Chinese dark tea. Thus, we conducted high-performance liquid chromatography and nontargeted metabolomic to analyze the non-volatile metabolites of TMPF. Our results discovered that the amounts of ( -)-epigallocatechin gallate, ( -)-epigallocatechin, ( -)-epicatechin gallate, and ( -)-epicatechin were decreased significantly (p < 0.05) after TMPF. By using nontargeted metabolomic analysis, a total of 1733 ion features were detected. KEGG pathway enrichment analysis showed that TMPF had a significant impact on caffeine metabolism. Also, theophylline, 3-methylxanthine, and 1,3,7-trimethyluric acid were increased significantly after TMPF, which suggested that demethylation and oxidation reaction might be the main pathways of caffeine metabolism. This study provides a better understanding of the mechanism of TMPF during high-temperature for Chinese dark tea and lays a foundation for further research. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01098-9.

Effects and Mechanism of Action of Panax notoginseng Saponins on the Pharmacokinetics of Warfarin.

BACKGROUD: The interactions between Chinese herbs and drugs pose a great challenge to the combined clinical application of Chinese herbs and drugs. Chinese medicinal products contain complex pharmacologically active components that may influence the in vivo processes of drugs in a variety of ways. In China, drugs based on Panax ginseng total saponins (PNS) are often combined with warfarin for the treatment of cardiovascular diseases. OBJECTIVES: To assess the effects of Panax notoginseng saponins (PNS) on the pharmacokinetics of warfarin and its mechanism. METHOD: Blood was collected for the determination of the prothrombin time (PT) and international normalized ratio (INR) from rats treated with warfarin alone or with warfarin + PNS. The plasma concentration of warfarin was determined by high-performance liquid chromatography. Western blot was used to detect the expression of cytochrome P450 (CYP) enzymes. RESULTS: When warfarin and PNS were co-administered, the PT and INR increased compared to when warfarin was given alone. 72 hours after administration, compared to the warfarin alone group, the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups showed 110%, 122%, and 126% increases in PT, respectively (all P < 0.05), as well as 111%, 124%, and 128% increases in INR (all P < 0.05). Compared with the warfarin alone group, the clearance rate (CL/F) of warfarin in the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups was 10% (P > 0.05), 23% (P < 0.05), and 33% (P < 0.05) lower, respectively, while the systemic exposure (area under the concentration-time curve, AUC0-t) increased by 106% (P > 0.05), 119% (P < 0.05), and 134% (P < 0.05), respectively, and the blood concentration of warfarin incresed by 112%, 113%, and 114%, respectively (all P > 0.05). After combined treatment of HepG2 cells with warfarin + PNS, CYP1A2 expression was upregulated (P < 0.05) and CYP3A4 was downregulated (P < 0.05) but there was no effect on CYP2C9. In animal experiments, PNS had different effect on the expression of CYP1A2 in different doses. While a low dose of PNS resulted in downregulated CYP1A2 expression (P < 0.05), a medium dose resulted in upregulation (P < 0.05), and CYP1A2 expression was not significantly affected by a high dose of PNS (P > 0.05). Meanwhile, PNS at all doses downregulated the expression of CYP3A4 (P < 0.05) but had no effect on the expression of CYP2C9 (P > 0.05). CONCLUSION: PNS can increase the blood concentration of warfarin, as well as the exposure time, and it can enhance the anticoagulant effect of warfarin by inhibiting the expression of the liver enzyme CYP3A4.

All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism.

Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.

Serum lipidomics reveals distinct metabolic profiles for asymptomatic hyperuricemic and gout patients.

OBJECTIVES: This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. METHODS: Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. RESULTS: In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. CONCLUSION: We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients.

An LC-MS/MS method for simultaneous quantification of 11 components of Xian-Xiong-Gu-Kang in the plasma of osteoarthritic rats and pharmacokinetic analysis.

Xian-Xiong-Gu-Kang is composed of Epimedium brevicornu, Ligusticum chuanxiong, Radix clematidis, Cinnamomum cassia, and Fructus xanthii. It is used to treat numbness and pain of limbs. In this study, we developed a method to simultaneously quantify 11 components of Xian-Xiong-Gu-Kang (icarrin, epimedin A, epimedin B, epimedin C, icariside II, chlorogenic acid, ligustilide, senkyunolide A, senkyunolide I, ferulic acid, and cinnamic acid) in rat plasma using ultra-performance liquid chromatography coupled with quadrupole linear ion trap mass spectrometry. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column using gradient elution with a mobile phase comprising acetonitrile and 0.05% (v/v) formic acid aqueous solution. Mass spectrometry detection was performed using positive and negative electrospray ionization in the multiple reaction monitoring mode. The calibration curves of the 11 constituents were linear, with correlation coefficients > 0.99. The intra- and interday accuracy and precision values were within ±15.0%. The extraction recoveries of the 11 constituents and two internal standards were between 66.05 and 105.40%, and the matrix effects were between 86.74 and 112.86%. Using this method, the pharmacokinetic features of the 11 constituents were elucidated in the plasma of osteoarthritic rats after oral administration of the Xian-Xiong-Gu-Kang extract.

Assessment of extrinsic and intrinsic influences on water quality variation in subtropical agricultural multipond systems.

Understanding wetland water quality dynamics and associated influencing factors is important to assess the numerous ecosystem services they provide. We present a combined self-organizing map (SOM) and linear mixed-effects model (LMEM) to relate water quality variation of multipond systems (MPSs, a common type of non-floodplain wetlands in agricultural regions of southern China) to their extrinsic and intrinsic influences for the first time. Across the 6 test MPSs with environmental gradients, ammonium nitrogen (NH4+-N), total nitrogen (TN), and total phosphate (TP) almost always exceeded the surface water quality standard (2.0, 2.0, and 0.4 mg/L, respectively) in the up- and midstream ponds, while chlorophyll-a (Chl-a) exhibited hypertrophic state (≥28 µg/L) in the midstream ponds during the wet season. Synergistic influences explained 69±12% and 73±10% of the water quality variations in the wet and dry season, respectively. The adverse, extrinsic influences were generally 1.4, 6.9, 3.2, and 4.3 times of the beneficial, intrinsic influences for NH4+-N, nitrate nitrogen (NO3--N), TP, and potassium permanganate index (CODMn), respectively, although the influencing direction and degree of forest and water area proportion were spatiotemporally unstable. While CODMn was primarily linked with rural residential areas in the midstream, higher TN and TP concentrations in the up- and midstream were associated with agricultural land, and NH4+-N reflected a small but non-negligible source of free-range poultry feeding. Pond surface sediments exhibited consistent, adverse effects with amplifications during rainfall, while macrophyte biomass can reflect the biological uptake of CODMn and Chl-a, especially in the mid- and downstream during the wet season. Our study advances nonpoint source pollution (NPSP) research for small water bodies, explores nutrient "source-sink" dynamics, and provides a timely guide for rural planning and pond management. The modelling procedures and analytical results can inform refined assessment of similar NFWs elsewhere, where restoration efforts are required.

Metabolite and Microbiome Profilings of Pickled Tea Elucidate the Role of Anaerobic Fermentation in Promoting High Levels of Gallic Acid Accumulation.

Gallic acid (GA) is an important active ingredient for its pharmacological activities. High levels of GA in tea can be obtained by anaerobic fermentation, but its mechanism is still unclear. Here, the profiles of metabolites and microbiomes in pickled tea were analyzed. The results showed that GA of pickled tea increased to 24.26 mg/g at 18 d after anaerobic fermentation, which was accompanied by the reducing levels of epicatechin gallate (ECG), epiafzelechin-3-O-gallate (EAG), and 7-galloylcatechin (7-GC) and the increasing relative abundances of Bacillus and other six bacterial genera. However, epigallocatechin gallate (EGCG) was basically stable during the whole fermentation process. These results suggested that EGCG contributes little to the GA formation during anaerobic fermentation, but ECG, EAG, and 7-GC should be the key precursors to form GA; moreover, bacteria, especially Bacillus, may be responsible for their bioconversion. It will establish an effective way to increase GA in tea production.

Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

OBJECTIVE: We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI. METHODS: The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Twenty-three RCTs involving 1712 patients with POI were included. Compared to hormone therapy (HT) groups, TKABP groups showed a significantly higher total effective rate (RR: 1.10; 95% CI: 1.04-1.17; P < 0.01, I 2 = 32%). In addition, TKABP groups revealed a better improvement in terms of serum follicle-stimulating hormone (FSH) levels, serum estradiol (E2) levels, peak systolic velocity (PSV) of ovarian stromal blood, and Kupperman index (KI) score. However, serum luteinizing hormone (LH) levels and ovarian volume (OV) showed no significant statistical difference. Subgroup analyses showed that herbal paste and 3 months of treatment duration had a greater effect on the improvement of hormone levels. Besides, the occurrence of related adverse events in TKABP groups was lower than that in HT groups. CONCLUSIONS: Our review suggests that TKABP appears to be an effective and safe measure for patients with POI, and the herbal paste may be superior. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with furthermore standardized researches of rigorous design.

Inhibition of NLRP3 inflammasome-mediated pyroptosis in macrophage by cycloastragenol contributes to amelioration of imiquimod-induced psoriasis-like skin inflammation in mice.

Psoriasis is a common chronic inflammatory skin disease, and the infiltrated macrophages in psoriatic skin lesions play a key role in the progression of this uncontrolled cutaneous inflammation. However, the current therapeutic strategies for patients with psoriasis are not satisfactory. Here, we report that cycloastragenol (CAG), a natural active small compound isolated from Astragalus membranaceus, significantly ameliorated imiquimod (IMQ)-induced psoriasiform dermatitis in mice by targeting proinflammatory macrophages. CAG significantly reduced the clinical scores, decreased the epidermal thickness, and ameliorated the deteriorating histopathology observed in IMQ-induced mice. CAG treatment specifically reduced the dermal infiltration of macrophages, rather than of dendritic cells, neutrophils, or T lymphocytes, into psoriatic skin. CAG dose-dependently decreased the level of proinflammatory cytokines, including IL-1ß, TNF-α and IL-6, in murine psoriatic skin and serum, as well as in IMQ-stimulated, bone-marrow-derived macrophages. When compared to the control group, CAG significantly decreased IMQ-triggered NLRP3 inflammasome activation and gasdermin D-mediated cell pyroptosis in these proinflammatory macrophages. CAG also suppressed the assembly of the NLRP3 inflammasome complex. Taken together, the results show that CAG selectively modulates macrophage function by inhibiting NLRP3 inflammasome-mediated pyroptosis to ameliorate IMQ-induced psoriasis-like skin inflammation in mice. Our findings also identify an effective drug candidate for the treatment of psoriasis.

Effect of bisphosphonates on overall survival in subgroups of patients with prostate cancer.

Adjuvant therapy with bisphosphonates in prostate cancer is effective in improving bone mineral density and thus reducing fractures and skeletal-related events. We analyzed the effect of bisphosphonates on overall survival (OS) in subgroups of patients with prostate cancer. A systematic literature search was conducted of the PubMed database and the bibliographies of related studies. The long-term OS rates were extracted from every eligible trial. The hazard ratio (HR) was pooled with the fixed effects model, and preplanned subgroup analyses were performed. The search yielded 112 articles, of which 10 articles with 13 patient subgroups met the eligibility criteria. The meta-analysis of all 13 subgroups showed that adjuvant bisphosphonate therapy did not significantly improve OS versus the control group (HR = 0.961, 95% CI 0.899-1.026, p = 0.233) with low heterogeneity (I2 = 13.47%, degrees of freedom = 12, p = 0.336). There was no significant improvement in OS with the addition of bisphosphonates in the major subgroup analyses (metastatic (M1) versus non-metastatic, clodronate versus zoledronic acid, castration-sensitive prostate cancer (CSPC) versus castration-refractory prostate cancer). When the subgroups were further divided, adjuvant bisphosphonate therapy significantly improved OS in patients with CSPC + M1 (HR = 0.874, 95% CI 0.778-0.982, p = 0.023; I2 = 0.0%, degrees of freedom = 3, p = 0.579). Our study demonstrated that bisphosphonates do not significantly improve long-term OS in patients with prostate cancer. However, adjuvant bisphosphonate therapy significantly improves OS in the subgroup of patients with CSPC + M1.

Serum Concentrations of 15 Elements Among Helicobacter Pylori-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China.

Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205 µg/L, P = 0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.

Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of acupuncture combined with Madopar for the treatment of Parkinson's disease (PD), compared to the use of Madopar alone. METHODS: A systematic search was carried out for randomised controlled trials (RCTs) of acupuncture and Madopar for the treatment of PD published between April 1995 and April 2015. The primary outcome was total effectiveness rate and secondary outcomes included Unified Parkinson's Disease Rating Scale (UPDRS) scores. Data were pooled and analysed with RevMan 5.3. Results were expressed as relative ratio (RR) with 95% confidence interval (CIs). RESULTS: Finally, 11 RCTs with 831 subjects were included. Meta-analyses showed that acupuncture combined with Madopar for the treatment of PD can significantly improve the clinical effectiveness compared with Madopar alone (RR=1.28, 95% CI 1.18 to 1.38, P<0.001). It was also found that acupuncture combined with Madopar significantly improved the UPDRS II (SMD=-1.00, 95% CI -1.71 to -0.29, P=0.006) and UPDRS I-IV total summed scores (SMD=-1.15, 95% CI -1.63 to -0.67, P<0.001) but not UPDRS I (SMD=-0.37, 95% CI -0.77 to 0.02, P=0.06), UPDRS III (SMD=-0.93, 95% CI -2.28 to 0.41, P=0.17) or UPDRS IV (SMD=-0.78, 95% CI -2.24 to 0.68, P=0.30) scores. Accordingly, acupuncture combined with Madopar appeared to have a positive effect on activities of daily life and the general condition of patients with PD, but was not better than Madopar alone for the treatment of mental activity, behaviour, mood and motor disability. In the safety evaluation, it was found that acupuncture combined with Madopar was associated with significantly fewer adverse effects including gastrointestinal reactions (RR=0.38, 95% CI 0.23 to 0.65, P<0.001), on-off phenomena (RR=0.27, 95% CI 0.11 to 0.66, P=0.004) and mental disorders (RR=0.24, 95% CI 0.06 to 0.92, P=0.04) but did not significantly reduce dyskinesia (RR=0.64, 95% CI 0.35 to 1.16, P=0.14). CONCLUSION: Acupuncture combined with Madopar appears, to some extent, to improve clinical effectiveness and safety in the treatment of PD, compared with Madopar alone. This conclusion must be considered cautiously, given the quality of most of the studies included was low. Therefore, more high-quality, multicentre, prospective, RCTs with large sample sizes are needed to further clarify the effect of acupuncture combined with Madopar for PD.