Screening for Active Compounds of Acorus calamus against SARS-CoV-2 Viral Protease and Mechanism Prediction.

COVID-19, caused by SARS-CoV-2, has emerged as the most destructive emerging infectious disease of the 21st century. Vaccination is an effective method to combat viral diseases. However, due to the constant mutation of the virus, new variants may weaken the efficacy of vaccines. In the current field of new coronavirus research, viral protease inhibitors have emerged as a highly regarded therapeutic strategy. Nevertheless, existing viral protease inhibitors do not fully meet the therapeutic needs. Therefore, this paper turned to traditional Chinese medicine to explore new active compounds. This study focused on 24 isolated compounds from Acorus calamus L. and identified 8 active components that exhibited significant inhibitory effects on SARS-CoV-2 PLpro. Among these, the compound 1R,5R,7S-guaiane-4R,10R-diol-6-one demonstrated the best inhibitory activity with IC50 values of 0.386 ± 0.118 µM. Additionally, menecubebane B and neo-acorane A exhibited inhibitory activity against both Mpro and PLpro proteases, indicating their potential as dual-target inhibitors. The molecular docking results confirmed the stable conformations of these compounds with the key targets and their good activity. ADMET and Lipinski's rule analyses revealed that all the small molecule ligands possessed excellent oral absorption properties. This study provides an experimental foundation for the discovery of promising antiviral lead compounds.

Effect of electroacupuncture on global cerebral ischemia-reperfusion injury in rats: A urine proteome analysis.

BACKGROUND: This study aimed to investigate dynamic urinary proteome changes of electroacupuncture (EP) on cerebral ischemia-reperfusion (CI/R) injured rats and to explore the therapeutic biological mechanisms of EP. METHODS: First, changed urinary proteins were found in EP stimulation in healthy rats. Then, we used a CI/R injury rat model induced by Pulsinelli's four-vessel occlusion (4-VO) method to explore the function of EP on urinary proteome in CI/R injury. Urine samples were collected for proteome analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. RESULTS: In total, 384 proteins were identified, among which 47 proteins (23 upregulated, 24 downregulated) were differentially expressed with 0.6-log FC and p < .05. Gene ontology analysis revealed that the cell redox homeostasis, acute-phase response, response to lipopolysaccharide, and cellular response to glucocorticoid stimulus were significantly enriched. The partially biologically connected differential proteins were found by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in the EP group. With the CI/R rat model, 80 proteins (27 upregulated, 53 downregulated) were significantly changed in the CI/R rats compared to the controls. Among these differentially expressed proteins (DEPs), 23 proteins (17 upregulated, six downregulated) showed significant changes after EP treatment (0.6-log FC change, p < .05). The main related biological processes were aging, immune response, acute-phase response, liver regeneration, protein catabolic process, and response to oxidative stress. Many metabolic pathways were enriched by KEGG analysis. CONCLUSION: Our results indicate that the EP could alleviate cerebral damage induced by ischemia-reperfusion through an anti-inflammatory and metabolism regulation mechanism. The urinary proteome might reflect the pathophysiological changes in EP pretreatment in the treatment and prevention of CI/R injury.

Lignans from the leaves of Styrax japonicus and their anti-inflammatory activity.

Five novel lignans, namely styraxjaponica A-E (1-5), together with eight known compounds (6-13) were isolated from the leaves of Styrax japonicus Siebold & Zucc. Their chemical structures were characterized by extensive analysis of 1D and 2D NMR, UV, IR, HRESIMS spectroscopic analysis as well as by comparison to the literature. The absolute configurations of the new compounds were further determined by quantum chemical electronic circular dichroism (ECD) calculations powered by time-dependent density functional theory (TDDFT). Moreover, the anti-inflammatory effects of compounds 1-5 in lipopolysaccharide (LPS)-induced RAW 264.7 cells were also evaluated by measuring nitric oxide (NO) concentrations. All compounds displayed significant anti-inflammatory activity without affecting cell viability in vitro.

Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

Zinc-glutathione in Chinese Baijiu prevents alcohol-associated liver injury.

Zinc depletion is associated with alcohol-associated liver injury. We tested the hypothesis that increasing zinc availability along with alcohol consumption prevents alcohol-associated liver injury. Zinc-glutathione (ZnGSH) was synthesized and directly added to Chinese Baijiu. Mice were administered a single gastric dose of 6 g/kg ethanol in Chinese Baijiu with or without ZnGSH. ZnGSH in Chinese Baijiu did not change the likeness of the drinkers but significantly reduced the recovery time from drunkenness along with elimination of high-dose mortality. ZnGSH in Chinese Baijiu decreased serum AST and ALT, suppressed steatosis and necrosis, and increased zinc and GSH concentrations in the liver. It also increased alcohol dehydrogenase and aldehyde dehydrogenase in the liver, stomach, and intestine and reduced acetaldehyde in the liver. Thus, ZnGSH in Chinese Baijiu prevents alcohol-associated liver injury by increasing alcohol metabolism timely with alcohol consumption, providing an alternative approach to the management of alcohol-associated drinking.

Melanin theranostic nanoplatform as an efficient drug delivery system for imaging-guided renal fibrosis therapy.

As renal fibrosis nanotherapeutics, the endogenous biomaterial melanin not only has natural biocompatibility and biodegradability but also has inherent photoacoustic imaging ability and certain anti-inflammatory effects. These properties determine that melanin can not only as a carrier of medication but also track the biodistribution and renal uptake of drugs in vivo by photoacoustic imaging in real-time. Curcumin is a natural compound with biological activity, which has excellent ROS scavenging ability and good anti-inflammatory property. These materials appear more advantages in the development of nanoscale diagnostic and therapeutic platforms for future clinical translation. Herein, this study developed curcumin-loaded melanin nanoparticles (MNP-PEG-CUR NPs) as an efficient medication delivery system for photoacoustic imaging guidance renal fibrosis treatment. The nanoparticles are about 10 nm in size, exhibit good renal clearance efficiency, excellent photoacoustic imaging ability, and good in vitro and in vivo biocompatibility. These preliminary results indicated that MNP-PEG-CUR have clinically applicable potential as a therapeutic nanoplatform for renal fibrosis.

An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

Optimization and comparison of nonconventional extraction techniques for soluble phenolic compounds from brocade orange (Citrus sinensis) peels.

Brocade orange (Citrus sinensis L. Osbeck) peels (BOPs) are rich in a variety of phenols with multiple and strong bioactivities. This study sought to utilize a response surface methodology to optimize the parameters of accelerated solvent extraction (ASE) to obtain phenolic extracts from BOPs. Total phenolic and flavonoid content (TPC and TFC), profiles, and antioxidant activities of extracts for free, esterified-, and glycosylated-bound phenols from ASE were compared with those derived from Soxhlet extraction (SE) (80°C, 6 h) and heat-reflux extraction (HRE) (80°C, 3 h). Maximum practical TPC and TFC under optimal ASE conditions (15 min, 108°C, 82 bar, and three cycles) were determined to be 32.82 mg gallic acid equivalents/dry weight (DW) and 10.25 mg rutin equivalents/DW, respectively. The profiles, contents, and corresponding bioactivities of the extracts significantly depended on extraction method, particularly with regard to phenolic fraction. Generally, ASE and HRE were associated with higher levels of extraction efficiency and higher quality targeted bioactive compounds with stronger antioxidant activity. More importantly, ASE represents a simple, efficient, and time-saving technique for the extraction of phenols. Furthermore, the finding that different phenolic fractions contain variable profiles and contents of phenols is useful for efforts to obtain targeted individual bioactive ingredients and make better use of biomass residues.

Transcription Profiling of a Revealed the Potential Molecular Mechanism of Governor Vessel Electroacupuncture for Spinal Cord Injury in Rats.

OBJECTIVE: This study aimed to identify differentially expressed genes (DEGs) by transcriptome analysis to elucidate a potential mechanism by which governor vessel electroacupuncture (GV-EA) promotes neuronal survival, axonal regeneration, and functional recovery after complete transection spinal cord injury (SCI). METHODS: Sham, control, or GV-EA group adult female Sprague Dawley rats underwent a complete transection SCI protocol. SCI area RNA-seq investigated the DEGs of coding and noncoding RNAs 7 days post-SCI. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were used to classify DEGs functions, to explain a possible molecular mechanism. Immunofluorescence and BBB (Basso, Beattie, and Bresnahan) score were used to verify a GV-EA treatment effect following SCI. RESULTS: GV-EA treatment could regulate the expression of 173 mRNA, 260 lncRNA, and 153 circRNA genes among these DEGs resulted by SCI. GO enrichment analysis showed that the DEGs were most enriched in membrane, actin binding, and regulation of Toll-like receptor signaling pathway. KEGG pathway analysis showed enriched pathways (e.g. , Toll-like receptors, MAPK, Hippo signaling). According to the ceRNA network, miR-144-3p played a regulatory role by interacting with lncRNA and circRNA. GV-EA also promoted the injured spinal cord neuron survival, axonal regeneration, and functional improvement of hind limb locomotion. CONCLUSION: Results of our RNA-seq suggest that post-SCI GV-EA may regulate characteristic changes in transcriptome gene expression, potential critical genes, and signaling pathways, providing clear directions for further investigation into the mechanism of GV-EA in subacute SCI treatment. Moreover, we found that GV-EA promotes neuronal survival, nerve fiber extension, and motor function recovery in subacute SCI.

[Spatial Distribution and Eco-stoichiometric Characteristics of Soil Nutrient Elements Under Different Vegetation Types in the Yellow River Delta Wetland].

To clarify the distribution characteristics and the ecological stoichiometric characteristics of nutrient elements in soils under different vegetation types, four typical natural wetlands, i.e., Phragmites australis wetland, Tamarix chinensis wetland, Suaeda salsa wetland, and Tidal flat wetland, as well as Gossypium spp. fields that were reclaimed from natural wetlands, were selected as study sites in the Yellow River Delta, and comparisons between the agricultural reclamation land and natural wetlands were conducted. The results showed that the soil total organic carbon (TOC) and total nitrogen (TN) contents in the natural wetlands were as follows:P. australis wetland and T. chinensis wetland>S. salsa wetland>Tidal flat, and the contents of TOC and TN were significantly negatively related to electrical conductivity (EC) and pH values (P<0.05). The contents of TOC, TN, and total phosphorus (TP) in Gossypium spp. fields were significantly higher than those in natural wetlands (P<0.05), especially the contents of nitrate nitrogen (NO3--N) in Gossypium spp. fields, which were 9.4-11.4 times that of natural wetlands. However, no significant correlations between TOC, TN, and TP and EC and pH values (P>0.05) were observed in Gossypium spp. fields. The results of correlation analysis showed that the C/N of natural wetlands were mainly controlled by the contents of TN (P<0.05), and the C/N of the Gossypium spp. fields were significantly lower than those of natural wetlands (P<0.05). The soil C/P and N/P of natural wetlands and Gossypium spp. fields in the Yellow River Delta were low, and the variation trends were consistent with those of soil TOC and TN. Comparative analysis revealed, on the whole, that there were significantly different soil nutrient element contents, C/N, C/P, and N/P in Gossypium spp. fields compared to those of natural wetlands (P<0.05). The process of reclamation could significantly change the spatial distribution of nutrient elements in wetlands. Our results should be of importance in revealing the biogeochemical process of soil nutrient elements in coastal wetland and the influence of agricultural reclamation activities on the differentiation of soil nutrient elements.

Mechanism of taurine reducing inflammation and organ injury in sepsis mice.

The fundamental basis for the pathogenesis of sepsis is an inflammatory imbalance, which is considered to be the main target for treatment. Taurine is an intracellular free amino acid that has anti-inflammatory and antioxidant effects. To investigate the protective mechanism of taurine in sepsis, we used in vitro and in vivo experiments to explore the effects of taurine on neutrophil and monocyte immune function. Metabolomic analysis showed large amounts of taurine in neutrophils and monocytes and a dramatic decrease in taurine levels after LPS exposure. Taurine supplementation decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) in LPS-challenged neutrophils and monocytes and reduced the formation of neutrophil extracellular traps by restricting reactive oxygen species. Moreover, taurine protected septic mice from death, improved tissue injuries in the lung, liver, and kidney by reducing neutrophil infiltration and TNF-α production. Our data indicate that a supplement with taurine might be a promising therapeutic strategy for sepsis to reduce hyper inflammation and improve multi-organ dysfunctions.

Preoperative laser reduces silicone oil use in primary diabetic vitrectomy.

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury.

Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI-AKI) remains unclear. Using single-cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte-derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9hi Ly6chi IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9+ macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small-molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long-term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI.

Electro-acupuncture and its combination with adult stem cell transplantation for spinal cord injury treatment: A summary of current laboratory findings and a review of literature.

The incidence and disability rate of spinal cord injury (SCI) worldwide are high, imposing a heavy burden on patients. Considerable research efforts have been directed toward identifying new strategies to effectively treat SCI. Governor Vessel electro-acupuncture (GV-EA), used in traditional Chinese medicine, combines acupuncture with modern electrical stimulation. It has been shown to improve the microenvironment of injured spinal cord (SC) by increasing levels of endogenous neurotrophic factors and reducing inflammation, thereby protecting injured neurons and promoting myelination. In addition, axons extending from transplanted stem cell-derived neurons can potentially bridge the two severed ends of tissues in a transected SC to rebuild neuronal circuits and restore motor and sensory functions. However, every single treatment approach to severe SCI has proven unsatisfactory. Combining different treatments-for example, electro-acupuncture (EA) with adult stem cell transplantation-appears to be a more promising strategy. In this review, we have summarized the recent progress over the past two decades by our team especially in the use of GV-EA for the repair of SCI. By this strategy, we have shown that EA can stimulate the nerve endings of the meningeal branch. This would elicit the dorsal root ganglion neurons to secrete excess amounts of calcitonin gene-related peptide centrally in the SC. The neuropeptide then activates the local cells to secrete neurotrophin-3 (NT-3), which mediates the survival and differentiation of donor stem cells overexpressing the NT-3 receptor, at the injury/graft site of the SC. Increased local production of NT-3 facilitates reconstruction of host neural tissue such as nerve fiber regeneration and myelination. All this events in sequence would ultimately strengthen the cortical motor-evoked potentials and restore the motor function of paralyzed limbs. The information presented herein provides a basis for future studies on the clinical application of GV-EA and adult stem cell transplantation for the treatment of SCI.

Multifunctional plasmonic gold nanostars for cancer diagnostic and therapeutic applications.

Gold nanostar (AuNSt) has gained great attention in bioimaging and cancer therapy due to their tunable surface plasmon resonance across the visible-near infrared range. Photothermal treatment and imaging capabilities including fluorescence lifetime imaging at two-photon excitation (TP-FLIM) and dark-field microscopic imaging are considered in this work. Two types of AuNSts having plasmon absorption peaks centred at 600 and 750 nm wavelength were synthesized and studied. Both NSts exhibited low cytotoxicity on A549 human lung carcinoma cells. A strong emission at two-photon excitation was observed for both NSts, well-distinguishable from lifetimes of bio-object autofluorescence. High efficiency in raising the temperature in the NSts environment with the irradiation of near infrared, AuNSts triggered photothermal effect. The decreased cell viability of A549 observed via MTT test and the cell membrane damaging was demonstrated with trypan blue staining. These results suggest AuNSts can be agents with tunable plasmonic properties for imaging and photothermal therapy.

Acupuncture combined with Chinese herbal medicine on non-alcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. However, there are no approved drugs for NAFLD. A number of studies have shown that acupuncture combined with Chinese herbal medicine (CHM) can be beneficial for NAFLD. However, high-quality trials are still lacking. Therefore, we aimed to conduct a systematic review and meta-analysis to assess the effectiveness and safety of acupuncture combined with CHM for NAFLD. METHODS: Eight electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database, and Wan-fang Database from inception to November 2021 will be searched. We will also search for Clinical Trials Registry Platforms as a supplement. Randomized controlled trials on acupuncture combined with CHM for NAFLD will be included. Literature screening, data extraction, and risk of bias assessment were independently conducted by 2 reviewers. All differences between the 2 reviewers will be discussed and resolved by a third reviewer. Revman5.3 software will be used for meta-analysis. RESULT: This study aimed to evaluate the effectiveness and safety of acupuncture combined with CHM for NAFLD. CONCLUSION: The findings of this study will provide more evidence to determine whether acupuncture combined with CHM for NAFLD is an effective and safe intervention for NAFLD.

Analysis of Acanthopanax giraldii Harms Polysaccharide II Composition and Its Immune-Protective Role in a Cyclophosphamide-Induced Immunosuppressive Mice Model.

Acanthopanax giraldii Harms is commonly used in traditional Chinese medicine to treat rheumatism, improve joints, and strengthen muscles and bones. The polysaccharides present in A. giraldii Harms contain major bioactive substances, which have antioxidant, anticancer, and antiviral activities. In this study, the structural characterization of the homogeneous polysaccharide isolated from A. giraldii Harms, known as AHP-II, and its immunomodulatory effects in vivo will be studied. High-performance ion chromatography (HPIC) and high-performance gel permeation chromatography (HPGPC) based analyses revealed that AHP-II was composed of various monosaccharides, which included rhamnose, arabinose, galactose, glucose, mannose, galacturonic acid, and glucuronic acid in molar ratios of 29.5 : 24.6 : 23.8 : 4.4 : 5.7 : 8.8 : 3.1, respectively, and had a collective molecular weight of 80.21 × 103 Da. Fourier-transform infrared (FTIR) spectroscopy indicated the presence of a pyranose ring and ß-type glycosidic linkages in AHP-II. In addition, immunomodulatory effect analyses of AHP-II that used a cyclophosphamide-induced immunosuppressive mouse model demonstrated that its treatment could significantly restore spleen and thymus indices, promote the proliferation of splenic lymphocytes, elevate CD4+ T lymphocyte percentage and CD4+ : CD8+ ratio in the spleen, promote macrophage phagocytosis, and restore cytokines (IL-6, TNF-α, IgM, and IgG) levels. These results suggested that AHP-II could potentially be used as natural immunomodulator and as an alternative treatment to reduce chemotherapy-induced immunosuppression.

A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the influenza A virus in vitro.

BACKGROUND: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 128 million people and has caused over 2.8 million deaths as of April 2021 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality. We investigated the potential anti-coronavirus activities from an oral liquid of traditional medicine, Respiratory Detox Shot (RDS), which contains mostly herbal ingredients traditionally used to manage lung diseases. RESULTS: Here we report that RDS inhibited the infection of target cells by lenti-SARS-CoV, lenti-SARS-CoV-2, and hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudoviruses, and by infectious SARS-CoV-2 and derived Ha-CoV-2 variants including B.1.1.7, B.1.351, P.1, B.1.429, B.1.2, B.1.494, B.1.1.207, B.1.258, and B.1.1.298. We further demonstrated that RDS directly inactivates the infectivity of SARS-CoV-2 virus particles. In addition, we found that RDS can also block the infection of target cells by Influenza A virus. CONCLUSIONS: These results suggest that RDS may broadly inhibit the infection of respiratory viruses.

Role of hsa­miR­105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer.

More than 70% of patients with epithelial ovarian cancer (EOC), one of the leading cause of gynecological cancer­related deaths worldwide, are diagnosed at an advanced stage of the disease. Currently, the mainstay for treatment of advanced EOC is tumor debulking surgery followed by combined platinum­ and paclitaxel (PTX)­based chemotherapy. However, most patients eventually develop chemoresistance, which remains a major obstacle to successful treatment. Herein, by using clinical specimens and experimentally induced cell models, we found that the expression levels of hsa­miR­105 were significantly decreased in PTX­resistant EOC tissues and cell lines. Follow­up functional experiments demonstrated that repression of hsa­miR­105 conferred resistance to paclitaxel in EOC cells, whereas restoration of hsa­miR­105 expression in situ via intratumoral injection of hsa­miR­105 micrON™ agomir potentiated in vivo sensitivity to PTX and thereafter significantly inhibited tumor growth in a PTX­challenged xenograft model. Mechanistically, hsa­miR­105 exerted its tumor suppressor function by directly inhibiting the zinc and ring finger 2 (ZNRF2) signaling pathway. Importantly, aberrant expression of hsa­miR­105 in both tumor and circulating samples predicted a poor post­chemotherapy prognosis in EOC patients. These findings collectively suggest that hsa­miR­105 may act as a potent tumor suppressor miRNA during the progression of EOC, likely affecting cell proliferation, invasiveness and chemosensitivity to PTX, and functioning at least in part via inhibition of ZNRF2 signaling. The stability and availability and ease in measurement of circulating hsa­miR­105 make it a valuable diagnostic/prognostic biomarker candidate for chemotherapy of EOC.

Electroacupuncture facilitates the integration of a grafted TrkC-modified mesenchymal stem cell-derived neural network into transected spinal cord in rats via increasing neurotrophin-3.

AIMS: This study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin-3 (NT-3) from injured spinal cord tissue, and, if so, whether the increased NT-3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)-modified mesenchymal stem cell (MSC)-derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord. METHODS: After NT-3-modified Schwann cells (SCs) and TrkC-modified MSCs were co-cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron-like cells that formed a MSC-derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks. RESULTS: Electroacupuncture application enhanced the production of endogenous NT-3 in damaged spinal cord tissues. The increase in local NT-3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT-3 high-affinity TrkC. The combination of MN implantation and EA application improved cortical motor-evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment. CONCLUSIONS: Electroacupuncture as an adjuvant therapy for TrkC-modified MSC-derived MN, acted by increasing the local production of NT-3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI.