The water extracts from the oil cakes of Prinsepia utilis repair the epidermal barrier via up-regulating Corneocyte Envelope-proteins, lipid synthases, and tight junction proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.

Restoration of Intestinal Microbiota After Inulin Supplementation Halted: The Secondary Effect of Supplemented Inulin.

SCOPE: Consumption of inulin could affect the intestinal microbiota composition. Hereby, it is aimed to investigate the intestinal microbial community restoration process when the inulin supplementation is terminated (i.e., the secondary effect). METHODS AND RESULTS: The current study investigates the response and restoration of intestinal microbiota to/after high (Inulin-H) and low (Inulin-L) dosage of inulin supplementation or sequential antibiotics and inulin (Anti-Inulin-L) supplementation, based on analysis of 16S rRNA gene sequences in C57BL/6 mice. The number of significantly changed genera in response to inulin is highest in Anti-Inulin-L (n = 66) group, followed by Inulin-H (n = 51) and Inulin-L (n = 38) group. After inulin supplementation stops, microbiota of all studied groups tend to recover to their original states, with highest percentage of inulin-responding microbes stay significantly different at Anti-Inulin-L (93.94%) group, followed by Inulin-H (74.51%) and Inulin-L (44.12%) groups. Of note, the relative abundance of some non-inulin-responding taxa significantly increases during restoration. CONCLUSION: Sequential antibiotics and inulin supplementation induce greatest changes in the intestinal microbial composition, followed by high and low dosage of inulin. Additionally, the changes induce by supplemented inulin in the intestinal microbial community, provide a chance for some microbes to outcompete the other microbes during the spontaneous restoration.

Near-Infrared-Responsive Rare Earth Nanoparticles for Optical Imaging and Wireless Phototherapy.

Near-infrared (NIR) light is well-suited for the optical imaging and wireless phototherapy of malignant diseases because of its deep tissue penetration, low autofluorescence, weak tissue scattering, and non-invasiveness. Rare earth nanoparticles (RENPs) are promising NIR-responsive materials, owing to their excellent physical and chemical properties. The 4f electron subshell of lanthanides, the main group of rare earth elements, has rich energy-level structures. This facilitates broad-spectrum light-to-light conversion and the conversion of light to other forms of energy, such as thermal and chemical energies. In addition, the abundant loadable and modifiable sites on the surface offer favorable conditions for the functional expansion of RENPs. In this review, the authors systematically discuss the main processes and mechanisms underlying the response of RENPs to NIR light and summarize recent advances in their applications in optical imaging, photothermal therapy, photodynamic therapy, photoimmunotherapy, optogenetics, and light-responsive drug release. Finally, the challenges and opportunities for the application of RENPs in optical imaging and wireless phototherapy under NIR activation are considered.

Wireless Photoactivated Targeted Nanosystem for Oncotherapy Via Synergistic Effects of Hyperthermia/Redox Stress Amplification/GSK-3ß Activity Inhibition.

Highly soluble salts and gas mediated therapies are emerging antitumor strategies. However, the therapeutic efficacy remains restricted by difficulty in delivering them to the tumor site and poorly controlled release in deep tissues. Here, an intelligent wireless photoactivated targeted nanosystem is designed for delivering LiCl and H2 to tumors for therapy. LiCl causes cell death by inhibiting the activity of GSK-3ß. H2 selectively interacts with reactive oxygen species in the tumor, leading to redox stress, which induces apoptosis. The significant heat generated by the nanosystem not only kills tumor cells but also accelerates the dissolution of LiCl and the release of H2. The rapid dissolution of LiCl leads to a surge in intracellular osmotic pressure, which further intensifies the redox stress response and enhances the efficiency of therapy. The nanosystem shows efficient tumor therapeutic capability via synergistic effects of hyperthermia/redox stress amplification/GSK-3ß activity inhibition.

Effects of pile-fermentation on the aroma quality of dark tea from a single large-leaf tea variety by GC × GC-QTOFMS and electronic nose.

Aroma is one of the significant quality factors of dark tea (DT). However, for a single large-leaf tea variety, there are few studies analyzing the effect of pile-fermentation on the aroma quality of DT. The GC × GC-QTOFMS, electronic nose (E-nose) and GC-olfactometry (GC-O) techniques were employed to analysis the difference of tea products before and after pile-fermentation. A total of 149 volatile metabolites (VMs) were identified, with 92 VMs exhibiting differential characteristics. Among these, 31 VMs with OAV > 1.0 were found to be correlated with E-nose results (|r| > 0.8). Additionally, GC-O analysis validated seven major differential metabolites. Notably, naphthalene, 2-methylnaphthalene, and dibenzofuran were found to enhance the woody aroma, while (Z)-4-heptenal, 2-nonenal and 1-hexanol were associated with an increase in mushroom, fatty and sweet odors, respectively. Moreover, 1-octen-3-ol was linked to reducing pungent fishy smell. These findings could provide a certain theoretical basis for understanding the influence of pile-fermentation on the aroma quality of dark tea.

The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Black phosphorus quantum dots induced ferroptosis in lung cell via increasing lipid peroxidation and iron accumulation.

Black Phosphorus Quantum Dots (BP-QDs) have potential applications in biomedicine. BP-QDs may enter the body through the respiratory tract during grinding and crushing production and processing, causing respiratory toxicity. Ferroptosis is an oxidative, iron-dependent form of cell death. Here, respiratory toxicity of BP-QDs has been validated in mice and human bronchial epithelial cells. After 24 h of exposure to different doses (4-32 µg/mL) of BP-QDs, intracellular lipid peroxidation and iron overload occurred in Beas-2B cells. After 4 times exposures by noninvasive tracheal instillation at four doses [0, 0.25, 0.5 and 1 (mg/kg/48h)], all animals were sacrificed, organs were removed, processed for pathological examination and molecular analysis. Iron overload, glutathione (GSH) depletion and lipid peroxidation in the lung tissue of mice in the exposure group. Furthermore, based on the ferroptosis-associated protein and mRNA expression, it was hypothesized that BP-QDs induced ferroptosis through increasing intracellular free iron and polyunsaturated fatty acid synthesis. By comparing with previous studies, we speculate that primary cells generally are more sensitive to BP-QDs-induced damage than cancer cells. In summary, findings in the present study confirmed that BP-QDs induce ferroptosis via increasing lipid peroxidation and iron accumulation in vitro and in vivo.

A novel proxy to examine interspecific phosphorus facilitation between plant species.

Resource complementarity can contribute to enhanced ecosystem functioning in diverse plant communities, but the role of facilitation in the enhanced complementarity is poorly understood. Here, we use leaf manganese concentration ([Mn]) as a proxy for rhizosheath carboxylate concentration to explore novel mechanisms of complementarity mediated by phosphorus (P) facilitation. In pot experiments, we showed that mixtures involving Carex korshinskyi, an efficient P-mobilizing species, exhibited greater biomass and relative complementarity effect than combinations without C. korshinskyi on P-deficient soils. Compared with monocultures, leaf [Mn] and [P] of species that are inefficient at P mobilization increased by 27% and 21% when grown with C. korshinskyi (i.e. interspecific P facilitation via carboxylates) rather than next to another inefficient P-mobilizing species. This experimental result was supported by a meta-analysis including a range of efficient P-mobilizing species. Phosphorus facilitation enhanced the relative complementarity effect in low-P environments, related to a greater change in several facilitated species of their root morphological traits relative to those in monoculture. Using leaf [Mn] as a proxy, we highlight a vital mechanism of interspecific P facilitation via belowground processes and provide evidence for the pivotal role of P facilitation mediated by the plasticity of root traits in biodiversity research.

Regulation of bone and fat balance by Fructus Ligustri Lucidi in ovariectomized mice.

CONTEXT: Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys. OBJECTIVE: This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism. MATERIALS AND METHODS: The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs). RESULTS: The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs. CONCLUSIONS: FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP.

Xinyang Tablet attenuates chronic hypoxia-induced right ventricular remodeling via inhibiting cardiomyocytes apoptosis.

BACKGROUND: Hypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear. METHODS: The content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Sprague-Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson's trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining. RESULTS: XYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression. CONCLUSIONS: We concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury.

[Effect of Danzhi Xiaoyao Powder on behavior and mitochondrial morphology and function of anxiety model rats].

Danzhi Xiaoyao Powder is a classical prescription for anxiety. This study aims to analyze the effect of this medicine on mitochondrial morphology and function of anxiety rats and explore the mechanism of it against anxiety. Specifically, uncertain empty bottle drinking water stimulation(21 days) was employed to induce anxiety in rats. The elevated plus-maze test and open field test were respectively performed on the 7 th, the 14 th, and the 21 st days of the stimulation, so as to detect the anxiety-related protein index brain-derived neurotrophic factor(BDNF) and evaluate the anxiety level of animals. On this basis, the effect of this prescription on anxiety rats was preliminarily evaluated. After the behavioral test on the 21 st day, rats were killed and the brain tissues were separated for the observation of the mitochondrial morphology and the determination of mitochondrial function-related indicators and the adenosine 5'-monophosphate-activated protein kinase(AMPK) level. The results showed that Danzhi Xiaoxiao Powder could alleviate the anxiety-like behavior of rats, significantly increase the percentage of time in open arm in elevated plus-maze test and the ration of activity time in the central area of the field, dose-dependently raise the activity levels of respiratory chain complex Ⅰ,Ⅱ,Ⅲ and Ⅳ and the adenosine triphosphate(ATP) content, and elevate the levels of BDNF and phosphorylated AMPK(p-AMPK). Clear structure and intact morphology of mitochondrial cristae in medial prefrontal cortex cells and amygdala were observed in the Danzhi Xiaoyao Powder group. In summary, Danzhi Xiaoyao Powder exerts therapeutic effect on anxiety, and the mechanism is the likelihood that p-AMPK protects the structure and maintains the function of mitochondria.

Discovery of novel selenium-containing azole derivatives as antifungal agents by exploiting the hydrophobic cleft of CYP51.

Herein, we report the design, synthesis and evaluation of a novel series of diselenide and selenide derivatives as potent antifungal agents by exploiting the hydrophobic cleft of CYP51. Among all synthesized compounds, the most potent compound B01 with low cytotoxic and hemolysis effect exhibited excellent activity against C.alb., C.gla., C.par. and C.kru., as well as selected fluconazole-resistant strains. Moreover, compound B01 could reduce the biofilm formation of the FCZ-resistant C.alb. Subsequently, metabolic stability assays using liver microsomes demonstrated that compound B01 showed good profiles of metabolic stability. With superior pharmacological profile, compound B01 was advanced into in vivo bioactivity evaluation. In a murine model of systemic C.alb. infection, compound B01 significantly reduced fungal load of kidneys. Furthermore, compound B01 revealed relatively low acute toxicity and subacute toxicity in mice. In addition, docking study performed into C.alb. CYP51, showed the binding mode between C.alb. CYP51 and compound B01. Collectively, diselenides compound B01 can be further developed for the potential treatment of invasive fungal infections.

Construction of ssDNA-Attached LR-Chimera Involving Z-DNA for ZBP1 Binding Analysis.

The binding of proteins to Z-DNA is hard to analyze, especially for short non-modified DNA, because it is easily transferred to B-DNA. Here, by the hybridization of a larger circular single-stranded DNA (ssDNA) with a smaller one, an LR-chimera (involving a left-handed part and a right-handed one) with an ssDNA loop is produced. The circular ssDNAs are prepared by the hybridization of two ssDNA fragments to form two nicks, followed by nick sealing with T4 DNA ligase. No splint (a scaffold DNA for circularizing ssDNA) is required, and no polymeric byproducts are produced. The ssDNA loop on the LR-chimera can be used to attach it with other molecules by hybridization with another ssDNA. The gel shift binding assay with Z-DNA specific binding antibody (Z22) or Z-DNA binding protein 1 (ZBP1) shows that stable Z-DNA can form under physiological ionic conditions even when the extra ssDNA part is present. Concretely, a 5'-terminal biotin-modified DNA oligonucleotide complementary to the ssDNA loop on the LR-chimera is used to attach it on the surface of a biosensor inlaid with streptavidin molecules, and the binding constant of ZBP1 with Z-DNA is analyzed by BLI (bio-layer interferometry). This approach is convenient for quantitatively analyzing the binding dynamics of Z-DNA with other molecules.

Effect of hyperthermic intraperitoneal chemotherapy in combination with cytoreductive surgery on the prognosis of patients with colorectal cancer peritoneal metastasis: a systematic review and meta-analysis.

BACKGROUND: Peritoneal metastasis often occurs in patients with colorectal cancer peritoneal metastasis, and the prognosis is poor. A large body of evidence highlights the beneficial effects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is little consensus on the optimal treatment strategy for patients with colorectal cancer peritoneal metastasis. The purpose of this study is to evaluate the impact of CRS + HIPEC on survival and provide reference for the treatment of patients with colorectal cancer peritoneal metastasis. METHODS: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov databases were screened from inception of the review to March 11, 2022. Ten studies were included in qualitative and quantitative analysis. RESULTS: A total of 3200 patients were enrolled in the study, including 788 patients in the CRS and HIPEC groups and 2412 patients in the control group, of which 3 were randomized controlled trials and 7 were cohort studies. The 3 randomized controlled studies were of high quality, and the quality scores of the 7 cohort studies were all 7 or above, indicating high quality. The results showed that the OS of CRS + HIPEC group was higher than that of control group (HR: 0.53, 95% CI: 0.38-0.73; P < 0.00001, I2 = 82.9%); the heterogeneity of the studies was large. The subgroup analysis showed that the OS of CRS and HIPEC group was higher than that of PC group (HR: 0.37, 95% CI: 0.30-0.47; P = 0.215, I2 = 31%) and higher than that in CRS group (HR: 0.73, 95% CI: 0.49-1.07; P = 0.163, I2 = 44.8%); the heterogeneity of the studies was low. In the OPEN group, the OS of THE CRS and HIPEC groups was higher than that in the control group (HR: 0.51, 95% CI: 0.38-0.70; P = 0.353, I2 = 3.9%); OPEN group showed lower heterogeneity. The OS of 60-100-min group was higher than that in the control group (HR: 0.65, 95% CI: 0.49-0.88; P = 0.172, I2 = 37.4%); the heterogeneity of the studies was low. Sensitivity analysis showed that there was no significant difference in the results of the combined analysis after each study was deleted. The results of publication bias showed that the P-value of Egger and Begg tests was 0.078 > 0.05, indicating that there is no publication bias. CONCLUSIONS: CRS + HIPEC can improve the survival rate of patients with colorectal cancer peritoneal metastasis.

Gut modulatory effects of flaxseed derived Maillard reaction products in Sprague-Dawley rats during sub-chronic toxicity.

Our study aimed to understand the effects of Maillard reaction products (MRPs) intake on intestinal health, in vitro digestion, and fermentation metabolites in Sprague-Dawley (SD) rats. MRPs promoted the digestion of pepsin, but was not conducive to the subsequent in vitro digestion of trypsin. MRPs ingestion increased the propionate in intestine, but it could not change the branched-chain fatty acids (BCFAs) and short-chain fatty acids (SCFAs). However, MRPs ingestion led to an increase in the Lactobacillus abundance in gut. In the high-dose groups, the abundance of genes in partial amino acid and monosaccharide metabolism increased, while in lipid metabolism decreased compared with the middle dose groups. Therefore, the absorption of MRPs was lowered than that of protein and carbohydrates. Through functional predictive analysis, our study could reveal the effects of long-term intake of MRPs on intestinal health in SD rats.

FvWRKY48 binds to the pectate lyase FvPLA promoter to control fruit softening in Fragaria vesca.

The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.

Anti-osteoporosis effect of Semen Cuscutae in ovariectomized mice through inhibition of bone resorption by osteoclasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae, called Tu-si-zi in Chinese, is a kind of dried mature seed in the Convolvulaceae family. It mainly distributes in China, Korea, Pakistan, Vietnam, India and Thailand. It is used as a kidney-tonifying drug for treatment of aging related diseases such as osteoporosis in traditional Chinese medicine. However, the exact mechanisms on bone resorption are poorly studied. AIM OF THE STUDY: The aim of this study was to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect. MATERIALS AND METHODS: Qualitative and quantitative analyses of Semen Cuscutae were performed by UPLC-Q-TOF-MS and HPLC-MS/MS, respectively. Changes in bone mineral density (BMD) induced by OVX in mice were measured by dual-energy X-ray absorptiometry and micro-computed tomography (µCT). Tartrate-resistant acid phosphatase (TRAP) staining as well as hematoxylin and eosin (HE) staining were used to observe bone microarchitectural changes. ELISA kits were used to assess the therapeutic effects of Semen Cuscutae on the serum levels of osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP-5b), and receptor activator of nuclear factor-κB (RANKL). The effect of Semen Cuscutae on primary cell viability was assessed using CCK-8 and anti-tartrate phosphatase assays. TRAP staining and actin ring staining were used to observe the effect of Semen Cuscutae on osteoclast differentiation. Western blotting was used to measure the effects of Semen Cuscutae on expressions of NFATC1, c-Src kinase, and c-fos. RESULTS: Results from UPLC-Q-TOF-MS showed that the main components of Semen Cuscutae were flavonoid compounds that included quercitrin, quercetin, hyperoside, caffeic acid, rutin, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercetin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, and astragalin. After the Semen Cuscutae extract was orally administered to OVX mice, bone density increased (P < 0.01) and bone microstructure was significantly improved (P < 0.01 or 0.05). Additionally, Semen Cuscutae exhibited a significant descending effect in the levels of serum TRACP-5b and RANKL, while there was a significant increase in OPG in the Semen Cuscutae group compared with the OVX group, especially at high doses. Moreover, we found that increasing of c-fos, c-Src kinase, and NFATC1 protein expressions were reversed by Semen Cuscutae in vitro and in vivo. CONCLUSIONS: Our results showed that Semen Cuscutae exhibited anti-osteoporosis effects through the c-fos/c-Src kinase/NFATC1 signaling pathway.

Molecular Mechanism of Nardostachyos Radix et Rhizoma-Agrimoniae Herba in Treatment of Arrhythmia Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).