Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Effects of Sophora flavescens aiton and the absorbed bioactive metabolite matrine individually and in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cells in nude mice.

Background: Sophora flavescens aiton (SFA) and its main bioactive metabolite matrine are widely used in traditional Chinese medicine (TCM) preparations and have achieved good curative effects for the treatment of various tumors. However, the mechanisms underlying SFA and matrine individually and in combination with chemotherapeutic drugs for treatment of gastric cancer (GC) remain unclear. Aim of the study: To elucidate the mechanisms underlying the ability of SFA and matrine individually and in combination with chemotherapeutic drugs to inhibit proliferation and promote apoptosis of human GC cells. Materials and methods: Forty-eight nude mice were randomly divided into six groups that were treated with normal saline (model group), 5-fluorouracil (5-FU), SFA decoction (SFAD), matrine, SFAD+5-FU, or matrine+5-FU. A subcutaneous heterotopic tumor model was established in nude mice by implantation of human GC BGC-823 cells. All mice were treated for 28 days. Bioactive metabolites in SFA were determined by HPLC-MS/MS. The tumor volume, tumor weight, and tumor inhibition rate of mice were documented. Histopathology and ultramicroscopic pathology of tumor tissues were observed. The tumor cell cycle and apoptosis in vivo were detected. Serum levels of PCNA, BAX, Bcl-2, Caspase-9, Caspase-3 and cleaved Caspase-3 were measured. Protein levels of MS4A10, MS4A8, MS4A7, PCNA, BAX, Bcl-2, Caspase-3, and cleaved Caspase-3 were measured in tumor tissues. Results: Both SFAD and matrine inhibited the growth of transplanted GC cells, which was more effective when combined with 5-FU. The tumor inhibition rates of the 5-FU, SFAD, matrine, SFAD+5-FU, and matrine+5-FU groups were 53.85%, 33.96%, 30.44%, 59.74%, and 56.55%, respectively. The body weight of tumor-bearing nude mice was greater in the SFAD group than the normal saline and matrine groups. SFAD+5-FU and matrine+5-FU blocked BGC-823 cells in the G0-G1/S transition, promoted apoptosis, and significantly decreased the content of serum apoptosis-inhibitory proteins (PCNA and Bcl-2) as well as protein expression of MS4A8, MS4A10, Bcl-2, and PCNA in tumor tissues, while increasing serum levels of pro-apoptotic proteins (Caspase-9, Caspase-3 and cleaved-Caspase-3) and protein expression of BAX and cleaved-Caspase-3 in tumor tissues. Conclusion: SFAD and matrine both individually and in combination with 5-FU ameliorated malignancy of transplanted tumors by reducing proliferation and promoting apoptosis of BGC-823 cells. These findings confirm the anti-tumor synergistic effect of TCM and chemotherapeutic drugs.

Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance.

Fungi play an irreplaceable role in drug discovery in the course of human history, as they possess unique abilities to synthesize diverse specialized metabolites with significant medicinal potential. Trichoderma are well-studied filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced by Trichoderma have gained extensive attention since they possess attractive chemical structures with remarkable biological activities. A large number of metabolites have been isolated from Trichoderma species in recent years. A previous review by Reino et al. summarized 186 compounds isolated from Trichoderma as well as their biological activities up to 2008. To update the relevant list of reviews of secondary metabolites produced from Trichoderma sp., we provide a comprehensive overview in regard to the newly described metabolites of Trichoderma from the beginning of 2009 to the end of 2020, with emphasis on their chemistry and various bioactivities. A total of 203 compounds with considerable bioactivities are included in this review, which is worth expecting for the discovery of new drug leads and agrochemicals in the foreseeable future. Moreover, new strategies for discovering secondary metabolites of Trichoderma in recent years are also discussed herein.

New Enantiomers of a Nor-Bisabolane Derivative and Two New Phthalides Produced by the Marine-Derived Fungus Penicillium chrysogenum LD-201810.

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)-1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)-1 by chiral HPLC successfully afforded individual enantiomers (+)-1 and (-)-1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)-1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1-7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 µg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

CONTEXT: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear. OBJECTIVE: To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS. SETTING AND DESIGN: The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks. RESULTS: Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism. CONCLUSIONS: Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.

Characterization of Peptacetobacter hominis gen. nov., sp. nov., isolated from human faeces, and proposal for the reclassification of Clostridium hiranonis within the genus Peptacetobacter.

A novel, Gram-stain-positive, rod-shaped, non-motile, non-spore-forming, obligately anaerobic bacterium, designated strain ZHW00191T, was isolated from human faeces and characterized by using a polyphasic taxonomic approach. Growth occurred at 25-45 °C (optimum, 37-42 °C), at pH 5.5-10.0 (optimum, pH 6.5-7.0) and with 0-2 % (w/v) NaCl (optimum, 0 %). The end products of glucose fermentation were acetic acid, isobutyric acid and isovaleric acid and a small amount of propionic acid. The dominant cellular fatty acids (>10 %) of strain ZHW00191T were C16 : 0, C18 : 1 ω9с and C18 : 2ω6,9с. Its polar lipid profile comprised diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids and ten unidentified glycolipids. Respiratory quinones were not detected. The cell-wall peptidoglycan contained meso-2,6-diaminopimelic acid, and the whole-cell sugars were ribose and glucose. The genomic DNA G+C content was 32.8 mol%. Analysis of the 16S rRNA gene sequence indicated that ZHW00191T was most closely related to Clostridium hiranonis TO-931T (95.3 % similarity). Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) analyses with closely related reference strains indicated that reassociation values were both well below the thresholds of 95-96% and 70 % for species delineation, respectively. Based on phenotypic, chemotaxonomic and genetic studies, a novel genus, Peptacetobacter gen. nov., is proposed. The novel isolate ZHW00191T (=JCM 33482T=GDMCC 1.1530T) is proposed as the type strain of the type species Peptacetobacter hominis gen. nov., sp. nov. of the proposed new genus. Furthermore, it is proposed that Clostridium hiranonis be transferred to this novel genus, as Peptacetobacter hiranonis comb. nov.

Understanding mercury methylation in the changing environment: Recent advances in assessing microbial methylators and mercury bioavailability.

Methylmercury (MeHg) is a neurotoxin, mainly derived from microbial mercury methylation in natural aquatic environments, and poses threats to human health. Polar regions and paddy soils are potential hotspots of mercury methylation and represent environmental settings that are susceptible to natural and anthropogenic perturbations. The effects of changing environmental conditions on the methylating microorganisms and mercury speciation due to global climate change and farming practices aimed for sustainable agriculture were discussed for polar regions and paddy soils, respectively. To better understand and predict microbial mercury methylation in the changing environment, we synthesized current understanding of how to effectively identify active mercury methylators and assess the bioavailability of different mercury species for methylation. The application of biomarkers based on the hgcAB genes have demonstrated the occurrence of potential mercury methylators, such as sulfate-reducing bacteria, iron-reducing bacteria, methanogen and syntrophs, in a diverse variety of microbial habitats. Advanced techniques, such as enriched stable isotope tracers, whole-cell biosensor and diffusive gradient thin film (DGT) have shown great promises in quantitatively assessing mercury availability to microbial methylators. Improved understanding of the complex structure of microbial communities consisting mercury methylators and non-methylators, chemical speciation of inorganic mercury under geochemically relevant conditions, and the pathway of cellular mercury uptake will undoubtedly facilitate accurate assessment and prediction of in situ microbial mercury methylation.

[A machine learning model based on initial gut microbiome data for predicting changes of Bifidobacterium after prebiotics consumption].

OBJECTIVE: To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake. METHODS: With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model. RESULTS: Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in ß diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01). CONCLUSION: Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.

Body size-dependent Cd accumulation in the zebra mussel Dreissena polymorpha from different routes.

Understanding body size-dependent metal accumulation in aquatic organisms (i.e., metal allometry) is critical in interpreting biomonitoring data. While growth has received the most attention, little is known about controls of metal exposure routes on metal allometry. Here, size-dependent Cd accumulation in zebra mussels (Dreissena polymorpha) from different routes were investigated by exposing mussels to A.(111Cd spiked algae+113Cd spiked river water) or B.(111Cd spiked sediments+113Cd spiked river water). After exposure, 111Cd or 113Cd levels in mussel tissue were found to be negatively correlated with tissue weight, while Cd allometry coefficients (b values) were dependent on Cd exposure routes: -0.664 for algae, -0.241 for sediments and -0.379 for river water, compared to -0.582 in un-exposed mussels. By comparing different Cd exposure routes, we found that size-dependent Cd bioaccumulation from algae or river water could be more responsible for the overall size-dependent Cd accumulation in mussels, and the relative importance of the two sources was dependent on mussel size ranges: Cadmium obtained from algae (algae-Cd) was more important in size-dependent Cd accumulation in smaller mussels (tissue dry weight < 5 mg), while river water-Cd became more important in larger individuals (tissue dry weight > 5 mg). In contrast, sediment-Cd contributed only a small amount to Cd accumulation in zebra mussels and may have little effect on size-dependent Cd bioaccumulation. Our results suggest that size-dependent Cd accumulation in mussels could be largely affected by exposure routes, which should be considered when trying to interpret Cd biomonitoring data of zebra mussels.