Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Nicotinamide Mononucleotide improves oocyte maturation of mice with type 1 diabetes.

BACKGROUND: The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN's effect. METHODS: Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes. RESULTS: The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes. CONCLUSION: NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.

Partial denitrifying phosphorus removal coupling with anammox (PDPRA) enables synergistic removal of C, N, and P nutrients from municipal wastewater: A year-round pilot-scale evaluation.

Applying anaerobic ammonium oxidation (anammox) in municipal wastewater treatment plants (MWWTPs) can unlock significant energy and resource savings. However, its practical implementation encounters significant challenges, particularly due to its limited compatibility with carbon and phosphorus removal processes. This study established a pilot-scale plant featuring a modified anaerobic-anoxic-oxic (A2O) process and operated continuously for 385 days, treating municipal wastewater of 50 m3/d. For the first time, we propose a novel concept of partial denitrifying phosphorus removal coupling with anammox (PDPRA), leveraging denitrifying phosphorus-accumulating organisms (DPAOs) as NO2- suppliers for anammox. 15N stable isotope tracing revealed that the PDPRA enabled an anammox reaction rate of 6.14 ± 0.18 µmol-N/(L·h), contributing 57.4 % to total inorganic nitrogen (TIN) removal. Metagenomic sequencing and 16S rRNA amplicon sequencing unveiled the co-existence and co-prosperity of anammox bacteria and DPAOs, with Candidatus Brocadia being highly enriched in the anoxic biofilms at a relative abundance of 2.46 ± 0.52 %. Finally, the PDPRA facilitated the synergistic conversion and removal of carbon, nitrogen, and phosphorus nutrients, achieving remarkable removal efficiencies of chemical oxygen demand (COD, 83.5 ± 5.3 %), NH4+ (99.8 ± 0.7 %), TIN (77.1 ± 3.6 %), and PO43- (99.3 ± 1.6 %), even under challenging operational conditions such as low temperature of 11.7 °C. The PDPRA offers a promising solution for reconciling the mainstream anammox and the carbon and phosphorus removal, shedding fresh light on the paradigm shift of MWWTPs in the near future.

Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation.

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

Biocompatible Ferrofluid-Based Millirobot for Tumor Photothermal Therapy in Near-Infrared-II Window.

Ferrofluidic robots with excellent deformability and controllability have been intensively studied recently. However, most of these studies are in vitro and the use of ferrofluids for in vivo medicinal applications remains a big challenge. The application of ferrofluidic robots to the body requires the solution of many key problems. In this study, biocompatibility, controllability, and tumor-killing efficacy are considered when creating a ferrofluid-based millirobot for in vivo tumor-targeted therapy. For biocompatibility problems, corn oil is used specifically for the ferrofluid robot. In addition, a control system is built that enables a 3D magnetic drive to be implemented in complex biological media. Using the photothermal conversion property of 1064 nm, the ferrofluid robot can kill tumor cells in vitro; inhibit tumor volume, destroy the tumor interstitium, increase tumor cell apoptosis, and inhibit tumor cell proliferation in vivo. This study provides a reference for ferrofluid-based millirobots to achieve targeted therapies in vivo.

Pyrrolizidine-producing weeds in tea gardens as an indicator of alkaloids in tea.

Pyrrolizidine alkaloids (PAs) can be transferred between plants via soil. Indicators of PAs in tea products are useful for tea garden management. In the present work a total of 37 weed species, 37 weed rhizospheric soils and 24 fresh tea leaf samples were collected from tea gardens, in which PAs were detected in 35 weeds species, 21 soil samples and 10 fresh tea leaves samples. In Shexian tea garden, 12.9 µg/kg of intermedine (Im) in one bud plus three leaves, 1.40 and 14.6 µg/kg of intermedine-N-oxide (ImNO) in one bud plus two leaves and one bud plus three leaves were detected, which were transferred from the PA-producing weeds via soil. However, no PAs were detected in fresh tea leaves collected from Langxi tea garden. The results indicated that synthesis of PAs in weeds and their transfer through the weed-soil-fresh tea leaf route varied with soil environments in different tea gardens.

Rheum officinale and Salvia miltiorrhiza inhibit renal fibrosis via miR-21/PTEN/Akt signaling pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the main components of many famous Chinese herbal formulas, Rheum palmatum L. and Salvia miltiorhiza Bunge (RS) are extensively used to treat chronic kidney disease (CKD). RS has been proved to improve renal function and relieve renal fibrosis (RF), but the potential mechanism remains a mystery. AIM OF THE STUDY: The purpose of this study is to determine whether microRNA-21 (miR-21) is associated with RF progression, as well as whether RS protects against RF through miR-21/PTEN/AKT signaling. MATERIALS AND METHODS: (1) The rat model of RF was established using unilateral ureteral obstruction (UUO). After UUO surgery, miR-21 levels in plasma were detected by RT-PCR and RF scores were assessed by Masson's trichrome stain at days 3, 7, 14 and 21. The correlation analysis of the above two indexes was carried out by Spearman correlation analysis. (2) Human proximal tubular epithelial cells (HK-2) was transfected with miR-21 mimic and inhibitor, and then the levels of phosphatase and tensin homolog (PTEN) protein and mRNA were measured with Western blotting and RT-PCR, respectively. (3) TGF-ß (10 ng/mL) was added into HK-2 cells to induce fibrosis, followed by the intervention of RS-containing rat serum. PTEN and protein kinase-B (Akt) phosphorylation, as well as the expression of PTEN protein in HK-2 cells, were assessed by RT-PCR, Western blotting and immunofluorescence. (4) The rat models of RF were prepared by UUO and treated with RS. Serum creatinine and urea nitrogen levels were measured. RF score was determined by Masson's trichrome stain. RT-PCR was used to determine the expression of miR-21, PTEN, and Akt mRNA. Western blotting was used to determine the expression of PTEN and Akt proteins. RESULTS: A positive correlation was found between plasma miR-21 levels and RF scores of rats after UUO surgery at Days 3, 7, 14 and 21. It was confirmed that miR-21 targeted PTEN. RS drug-containing serum could rise the expression of PTEN and reduce Akt phosphorylation of HK-2 cells induced by TGF-ß. Moreover, RS drug-containing serum could increase PTEN expression and reduce Akt phosphorylation induced by miR-21 mimic in HK-2 cells. The rats treated with RS had significantly decreased serum creatinine and urea nitrogen levels and a lower RF score. RS also decreased miR-21 and Akt expressions, increased PTEN expression of UUO rats. CONCLUSION: There was a positive correlation between plasma miR-21 levels and RF scores. The inhibitory effect of RS on RF might be mediated by miR-21/PTEN/AKT signaling.

Effect of a 4-Week Internet-Delivered Mindfulness-Based Cancer Recovery Intervention on the Symptom Burden and Quality of Life of Patients With Breast Cancer: Randomized Controlled Trial.

BACKGROUND: Mindfulness-based interventions (MBIs) can improve the symptoms and psychological well-being of patients with breast cancer. However, standard MBIs are an 8-week program delivered face-to-face, which may be inconvenient for patients with cancer. Many attempts have been made to adapt MBIs to increase their accessibility for patients with cancer while maintaining their therapeutic components and efficacy. OBJECTIVE: This study aimed to investigate the effectiveness of a 4-week internet-delivered mindfulness-based cancer recovery (iMBCR) program in reducing symptom burden and enhancing the health-related quality of life (HRQoL) of patients with breast cancer. METHODS: A total of 103 postoperative patients with breast cancer (stages 0 to IV) were randomly assigned to an iMBCR group (4-week iMBCR; n=51, 49.5%) or a control group (usual care and 4-week program of health education information; n=52, 50.5%). The study outcomes included symptom burden and HRQoL, as measured by the MD Anderson Symptom Inventory and the Functional Assessment of Cancer Therapy-Breast scale. All data were collected at baseline (T0), after the intervention (T1), and at 1-month follow-up (T2). Data analysis followed the intention-to-treat principle. Linear mixed models were used to assess the effects over time of the iMBCR program. RESULTS: Participants in the iMBCR group had significantly larger decreases in symptom burden than those in the control group at T1 (mean difference -11.67, 95% CI -16.99 to -6.36), and the decreases were maintained at T2 (mean difference -11.83, 95% CI -18.19 to -5.46). The HRQoL score in the iMBCR group had significantly larger improvements than that in the control group at T1 and T2 (mean difference 6.66, 95% CI 3.43-9.90 and mean difference 11.94, 95% CI 7.56-16.32, respectively). CONCLUSIONS: Our preliminary findings suggest that the iMBCR program effectively improved the symptom burden and HRQoL of patients with breast cancer, and the participants in the iMBCR group demonstrated good adherence and completion rates. These results indicate that the iMBCR intervention might be a promising way to reduce symptom burden and improve HRQoL of patients with cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038980; http://www.chictr.org.cn/showproj.aspx?proj=62659.

Source and Route of Pyrrolizidine Alkaloid Contamination in Tea Samples.

Toxic pyrrolizidine alkaloids (PAs) are found in tea samples, which pose a threat to human health. However, the source and route of PA contamination in tea samples have remained unclear. In this work, an adsorbent method combined with UPLC-MS/MS was developed to determine 15 PAs in the weed Ageratum conyzoides L., A. conyzoides rhizospheric soil, fresh tea leaves, and dried tea samples. The average recoveries ranged from 78%-111%, with relative standard deviations of 0.33%-14.8%. Fifteen pairs of A. conyzoides and A. conyzoides rhizospheric soil samples and 60 fresh tea leaf samples were collected from the Jinzhai tea garden in Anhui Province, China, and analyzed for the 15 PAs. Not all 15 PAs were detected in fresh tea leaves, except for intermedine-N-oxide (ImNO) and senecionine (Sn). The content of ImNO (34.7 µg/kg) was greater than that of Sn (9.69 µg/kg). In addition, both ImNO and Sn were concentrated in the young leaves of the tea plant, while their content was lower in the old leaves. The results indicated that the PAs in tea were transferred through the path of PA-producing weeds-soil-fresh tea leaves in tea gardens.

Upregulation of Succinate Dehydrogenase (SDHA) Contributes to Enhanced Bioenergetics of Ovarian Cancer Cells and Higher Sensitivity to Anti-Metabolic Agent Shikonin.

We discovered that the overexpression of mitochondrial enzyme succinate dehydrogenase (SDHA) is particularly prevalent in ovarian carcinoma and promotes highly metabolically active phenotype. Succinate dehydrogenase deficiency has been previously studied in some rare disorders. However, the role of SDHA upregulation and its impact on ovarian cancer metabolism has never been investigated, emphasizing the need for further research. We investigated the functional consequences of SDHA overexpression in ovarian cancer. Using proteomics approaches and biological assays, we interrogated protein content of metabolic pathways, cell proliferation, anchorage-independent growth, mitochondrial respiration, glycolytic function, and ATP production rates in those cells. Lastly, we performed a drug screening to identify agents specifically targeting the SDHA overexpressing tumor cells. We showed that SDHA overexpressing cells are characterized by enhanced energy metabolism, relying on both glycolysis and oxidative phosphorylation to meet their energy needs. In addition, SDHA-high phenotype was associated with cell vulnerability to glucose and glutamine deprivation, which led to a substantial reduction of ATP yield. We also identified an anti-metabolic compound shikonin with a potent efficacy against SDHA overexpressing ovarian cancer cells. Our data underline the unappreciated role of SDHA in reprogramming of ovarian cancer metabolism, which represents a new opportunity for therapeutic intervention.

The construction of preclinical evidence for the treatment of liver fibrosis with quercetin: A systematic review and meta-analysis.

Quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid, is widely found in fruits and vegetables and exerts broad-spectrum pharmacological effects in the liver. Many studies have explored the bioactivity of quercetin in the treatment of liver fibrosis. Hence, through a systematic review and biological mechanism evaluation, this study aimed to construct a body of preclinical evidence for the treatment of liver fibrosis using quercetin. The literature used in this study was mainly obtained from four databases, and the SYRCLE list (10 items) was used to evaluate the quality of the included literature. A meta-analysis of HA, LN, and other indicators was performed via STATA 15.0 software. Subgroup analyses based on animal species and model protocol were performed to further obtain detailed results. Moreover, the therapeutic mechanism of quercetin was summarized in a directed network form based on a comprehensive search of the literature. After screening, a total of 14 articles (comprising 15 studies) involving 254 animals were included. The results from the analysis showed that the corresponding liver function indexes, such as the levels of HA and LN, were significantly improved in the quercetin group compared with the model group, and liver function, such as the levels of AST and ALT, were also improved in the quercetin group. The species- and model-based subgroup analyses of AST and ALT revealed that quercetin exerts a significant effect. The therapeutic mechanism of quercetin was shown to be related to multiple pathways involving anti-inflammatory and antioxidant activities and lipid accumulation, including regulation of the TGF-ß, α-SMA, ROS, and P-AMPK pathways. The results showed that quercetin exerts an obvious effect on liver fibrosis, and more prominent improvement effects on liver function and liver fibrosis indicators were obtained with a dose of 5-200 mg during a treatment course ranging from 4 to 8 weeks. Quercetin might be a promising therapeutic for liver fibrosis.

Study on the Potential Molecular Mechanism of Xihuang Pill in the Treatment of Pancreatic Cancer Based on Network Pharmacology and Bioinformatics.

Objective: We aimed to analyze the possible molecular mechanism of Xihuang pill (XHP) in the treatment of pancreatic cancer based on methods of network pharmacology, molecular docking, and bioinformatics. Methods: The main active components and targets were obtained through the TCMSP database, the BATMAN-TCM database, and the Chemistry database. The active ingredients were screened according to the "Absorption, Distribution, Metabolism, Excretion" (ADME) principle and supplemented with literature. We searched GeneCards, OMIM, TTD, and DrugBank databases for pancreatic cancer targets. The targets of disease and ingredients were intersected to obtain candidate key targets. Then, we constructed a protein-protein interaction (PPI) network for protein interaction analysis and a composition-key target map to obtain essential effective ingredients. Metascape was used to perform functional enrichment analysis to screen critical targets and pathways. The expression and prognosis of key targets were examined and analyzed, and molecular docking was carried out. Results: A total of 52 active ingredients of XHP, 121 candidate targets, and 52 intersecting targets were obtained. The core active ingredients of XHP for the treatment of pancreatic cancer were quercetin, 17-ß-estradiol, ursolic acid, and daidzein. The core targets were EGFR, ESR1, MAPK1, MAPK8, MAPK14, TP53, and JUN, which were highly expressed genes of pancreatic cancer. Among them, EGFR and MAPK1 were significantly correlated with the survival of pancreatic cancer patients. The key pathway was the EGFR/MAPK pathway. The molecular docking results indicated that four active compositions had good binding ability to key targets. Conclusion: The molecular mechanism of XHP for the treatment of pancreatic cancer involved multiple components, multiple targets, and multiple pathways. This research theoretically elucidated the ameliorative effect of XHP against pancreatic cancer and might provide new ideas for further research on the treatment of pancreatic cancer.

Rapid detection of illegally added nifedipine in Chinese traditional patent medicine by surface-enhanced Raman spectroscopy.

Nifedipine is an antihypertensive chemical. The illegal addition of this chemical into Chinese traditional patent medicine (CTPM) is unstandardized and lacks regulation. It could bring serious side effects to patients, causing various symptoms. Therefore, accurate detection of nifedipine is very important for human health and the prevention of illegal additives. Surface-enhanced Raman spectroscopy (SERS) is a fast and sensitive fingerprint spectroscopic technique, which has been shown to be promising in drug detection. In this study, nifedipine in CTPM was determined qualitatively and quantitatively with SERS. Linear relationships between the concentrations of nifedipine and the intensities of the characteristic peaks were established. The results showed a linear relationship within the concentration range of 0.5-10 mg/L, and the lowest detectable concentration of nifedipine in CTPM was 0.1 mg/L (equivalent to 0.03% doping of nifedipine in CTPM). This method has shown a great potential in the detection of drugs illegally added to CTPM.

Therapeutic Targets of Bufalin on Renal Carcinoma and Mechanisms: Experimental Validation of Network Pharmacology Analysis.

The possible targets underlying the activity of bufalin on renal cell carcinoma (RCC) were investigated using network pharmacology and experimental approaches. PharmMapper and other databases were explored for predicting the bufalin targets and RCC-related targets. Finally, the enriched pathways and the targets were analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Furthermore, in vitro cell experiments were used to verify bufalin activation of AKT and MAPK signaling pathways in human mesangial cells. The therapeutic targets related to bufalin were identified via 35 intersecting targets. GO analysis identified 29 molecular functions, 16 cellular components, and 91 biological processes. KEGG pathway annotation identified 15 signal transduction pathways and 4 tumor-related pathways.

Exploring dynamic functional connectivity alterations in the preclinical stage of Alzheimer's disease: an exploratory study from SILCODE.

Objective.Exploring functional connectivity (FC) alterations is important for the understanding of underlying neuronal network alterations in subjective cognitive decline (SCD). The objective of this study was to prove that dynamic FC can better reflect the changes of brain function in individuals with SCD compared to static FC, and further to explore the association between FC alterations and amyloid pathology in the preclinical stage of Alzheimer's disease.Approach.A total of 101 normal control (NC) subjects, 97 SCDs, and 55 cognitive impairment (CI) subjects constituted the whole-cohort. Of these, 29 NCs and 52 SCDs with amyloid images were selected as the sub-cohort. First, independent components (ICs) were identified by IC analysis and static and dynamic FC were calculated by pairwise correlation coefficient between ICs. Second, FC alterations were identified through group comparison, and seed-based dynamic FC analysis was done. Analysis of variance was used to compare the seed-based dynamic FC maps and measure the group or amyloid effects. Finally, correlation analysis was conducted between the altered dynamic FC and amyloid burden.Main results.The results showed that 42 ICs were revealed. Significantly altered dynamic FC included those between the salience/ventral attention network, the default mode network, and the visual network. Specifically, the thalamus/caudate (IC 25) drove the hub role in the group differences. In the seed-based dynamic FC analysis, the dynamic FC between the thalamus/caudate and the middle temporal/frontal gyrus was observed to be higher in the SCD and CI groups. Moreover, a higher dynamic FC between the thalamus/caudate and visual cortex was observed in the amyloid positive group. Finally, the altered dynamic FC was associated with the amyloid global standardized uptake value ratio (SUVr).Significance.Our findings suggest SCD-related alterations could be more reflected by dynamic FC than static FC, and the alterations are associated with global SUVr.

Development of human iPSC-derived quiescent hepatic stellate cell-like cells for drug discovery and in vitro disease modeling.

Hepatic stellate cells (HSCs) play a central role in the progression of liver fibrosis by producing extracellular matrices. The development of drugs to suppress liver fibrosis has been hampered by the lack of human quiescent HSCs (qHSCs) and an appropriate in vitro model that faithfully recapitulates HSC activation. In the present study, we developed a culture system to generate qHSC-like cells from human-induced pluripotent stem cells (hiPSCs) that can be converted into activated HSCs in culture. To monitor the activation process, a red fluorescent protein (RFP) gene was inserted in hiPSCs downstream of the activation marker gene actin alpha 2 smooth muscle (ACTA2). Using qHSC-like cells derived from RFP reporter iPSCs, we screened a repurposing chemical library and identified therapeutic candidates that prevent liver fibrosis. Hence, hiPSC-derived qHSC-like cells will be a useful tool to study the mechanism of HSC activation and to identify therapeutic agents.

The effectiveness of herbal acupoint application for functional diarrhea: Protocol for a meta-analysis and data mining.

BACKGROUND: Functional diarrhea (FDr), one of the most common functional gastrointestinal diseases, is a kind of functional bowel disease characterized by repeated paste feces or watery feces. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of herbal acupoint application (HAA) on FDr. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: We will search the following 8 databases from their inception to October 15, 2021, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure. The primaryoutcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software (Available at: https://community.cochrane.org/help/tools-and-software/revman-5). Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the overall quality of evidence supporting the primary outcomes. We will also use SPASS software (Version 19.0 (Available at: https://www.ibm.com/analytics/spss-statistics-software)) for complex network analysis to explore the potential core prescription of acupoint herbal patching for FDr. RESULTS: This study will analyze the clinical effective rate, bristol stool scale, number of daily bowel movements, clinical symptom scale of diarrhea, and effective prescriptions of HAA for patients with FDr. CONCLUSION: The conclusion of our findings will provide evidence for the effectiveness and potential treatment prescriptions of HAA for patients with FDr.

[Network Meta-analysis of Chinese patent medicine in treatment of unstable angina pectoris].

Network Meta-analysis was used to compare the efficacy and safety of Chinese patent medicines in the treatment of unstable angina pectoris. PubMed, Cochrane Library, CNKI, Wanfang, VIP and other databases were retrieved by computers from the establishment of the databases to June 2020. Randomized controlled trials(RCTs) of Chinese patent medicines for the treatment of unstable angina pectoris were collected. Two investigators independently screened out the literatures, and extracted data according to the inclusion and exclusion criteria. The quality of the included RCTs was evaluated according to the bias risk assessment tool recommended by the Cochrane System Reviewer Manual, and the Stata 13.0 software was used for data analysis and mapping. Through screening, 28 eligible studies were finally included, with the sample size of 2 885 cases, involving 8 Chinese patent medicines. The results of the network Meta-analysis showed that in terms of total effective rate for angina symptom improvement, the order was as follows: Shenshao Capsules > Naoxintong Capsules > Ginkgo Ketone Ester Dripping Pills > Compound Danshen Dripping Pills > Ginkgo Leaf Tablets > Shexiang Baoxin Pills > Tongxinluo Capsules > Yindan Xinnaotong Soft Capsules; in terms of total effective rate for ECG curative effect, the order was as follows: Ginkgo Ketone Ester Dripping Pills>Compound Danshen Dripping Pills > Tongxinluo Capsules > Shenshao Capsules > Shexiang Baoxin Pills > Yindan Xinnaotong Soft Capsules; in terms of hypersensitivity-C-reactive protein curative effect, the order was as follows: Tongxinluo Capsules > Shenshao Capsules > Ginkgo Leaf Tablets>Compound Danshen Dropping Pills> Shexiang Baoxin Pills > Naoxintong Capsules > Yindan Xinnaotong Soft Capsules > Ginkgo Ketone Ester Dropping Pills. Chinese patent medicine combined with conventional therapy can improve the clinical efficacy of unstable angina pectoris. Due to the differences in the quantity and quality of the included studies, the order results of Chinese patent medicines need to be further verified.

[Research progresses in the biosynthesis of curcuminoids].

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.

Quercetin promotes osteogenic differentiation and antioxidant responses of mouse bone mesenchymal stem cells through activation of the AMPK/SIRT1 signaling pathway.

Decrepitude and apoptosis of bone mesenchymal stem cells (BMSCs) induced by reactive oxygen species (ROS) lead to inhibited osteogenic differentiation, causing decreased bone density and osteoporosis. Quercetin, a bioactive component of Solanum muricatum extracts, promotes the osteogenic differentiation of BMSCs and ameliorates the symptoms of osteoporosis in vivo. However, the detailed mechanism underlying this process remains unclear. The study aims to reveal the regulatory mechanism of quercetin in BMSCs. Mouse BMSCs (mBMSCs) were isolated from the bone marrow and characterized by flow cytometry. QRT-PCR and western blot assays were performed to evaluate the expression levels of related genes and proteins. Alkaline phosphatase (ALP) staining and Oil Red O staining of lipids were used to estimate the osteogenesis and adipogenesis levels of mBMSCs, respectively. Quercetin treatment (2 and 5 µM) induced significant upregulation of antioxidant enzymes, SOD1 and SOD2, in mBMSCs. Quercetin promoted osteogenic differentiation and inhibited adipogenic differentiation of mBMSCs. Quercetin treatment enhanced the phosphorylation of AMPK protein and upregulated the expression of SIRT1, thus activating the AMPK/SIRT1 signaling pathway in mBMSCs. Quercetin promoted osteogenic differentiation and antioxidant responses of mBMSCs by activating the AMPK/SIRT1 signaling pathway.