Occurrence of black queen cell virus in wild bumble bee communities in China.

Wild bumble bees (Hymenoptera: Apidae) play a vital role in agro-ecosystems as important pollinators. However, they are threatened by virus pathogens that are widespread in honey bees. Previous studies have reported that viruses were able to be transmitted across bee genera and caused potential danger to wild bumble bees. China is a global biodiversity hotspot for bumble bees. However, the impact of viruses on the wild bumble bee communities remains elusive. Black queen cell virus (BQCV) is one of the most common honey bee viruses. Here, a total of 72 wild bumble bee samples from 17 geographic regions of China were tested for BQCV. Thirteen positive samples were identified and sequence comparison of partial capsid genes demonstrated a genetic identity of 99.69% to 100%. A phylogenetic tree analysis also showed a close relationship between 13 BQCV isolates and others from a variety of recorded hosts in China. Meanwhile, a distinct evolutionary branch of China isolates was formed when clustering isolates from worldwide bumble bee species. A correlation between BQCV and their geographic locations were observed (P < 0.05). This study not only provides the first evidence of widespread BQCV in wild bumble bee communities in China but also detects a distinct set of genetically identical or closely related BQCV variants that circulate and evolutionarily differ from other countries.

Potential role of the gut microbiota of bumblebee Bombus pyrosoma in adaptation to high-altitude habitats.

The gut microbiota affects the health and overall fitness of bumblebees. It can enhance the host's ecological range by leveraging their metabolic capacities. However, the diversity of the gut microbiota and adaptive functional evolution in high-altitude regions remain unclear. To explore how the gut microbiota helps the host adapt to high-altitude environments, we analyzed the differences in diversity and function of the gut microbiota between high- and low-altitude regions through full-length 16S rRNA sequencing. Our results show that high-altitude regions have a lower abundance of Fructobacillus and Saccharibacter compared to low-altitude regions. Additionally, some individuals in low-altitude regions were invaded by opportunistic pathogens. The gut microbiota in high-altitude regions has a greater number of pathways involved in "Protein digestion and absorption" and "Biosynthesis of amino acids," while fewer carbohydrate pathways are involved in "digestion and absorption" and "Salmonella infection." Our finding suggests that plateau hosts typically reduce energy metabolism and enhance immunity in response to adverse environments. Correspondingly, the gut microbiota also makes changes, such as reducing carbohydrate degradation and increasing protein utilization in response to the host. Additionally, the gut microbiota regulates their abundance and function to help the host adapt to adverse high-altitude environments.

Precise nanodrug delivery systems with cell-specific targeting for ALI/ARDS treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and critical diseases in clinics and have no effective treatment to date. With the concept of "precision medicine", research into the precise drug delivery of therapeutic and diagnostic drugs has become a frontier in nanomedicine research and has entered the era of design of precise nanodrug delivery systems (NDDSs) with cell-specific targeting. Owing to the distinctive characteristics of ALI/ARDS, designing NDDSs for specific focal sites is an important strategy for changing drug distribution in the body and specifically increasing drug concentration at target sites while decreasing drug concentration at non-target sites. This strategy enhances drug efficacy, reduces adverse reactions, and ensures accurate nano-targeted treatment. On the basis of the characteristics of pathological ALI/ARDS microenvironments, this paper reviews NDDSs targeting vascular endothelial cells, neutrophils, alveolar macrophages, and alveolar epithelial cells to provide reference for designing accurate NDDSs for ALI/ARDS and novel insights into targeted treatments for ALI/ARDS.

Doxorubicin downregulates autophagy to promote apoptosis-induced dilated cardiomyopathy via regulating the AMPK/mTOR pathway.

The broad-spectrum antineoplastic drug doxorubicin (DOX) has one of the most serious chronic side effects on the heart, dilated cardiomyopathy, but the precise molecular mechanisms underlying disease progression subsequent to long latency periods remain puzzling. Here, we established a model of DOX-induced dilated cardiomyopathy. In a cardiac cytology exploration, we found that differentially expressed genes in the KEGG signaling pathway enrichment provided a novel complex network of mTOR bridging autophagy and oxidative stress. Validation results showed that DOX caused intracellular reactive oxygen species accumulation in cardiomyocytes, disrupted mitochondria, led to imbalanced intracellular energy metabolism, and triggered cardiomyocyte apoptosis. Apoptosis showed a negative correlation with DOX-regulated cardiomyocyte autophagy. To evaluate whether the inhibition of mTOR could upregulate autophagy to protect cardiomyocytes, we used rapamycin to restore autophagy depressed by DOX. Rapamycin increased cardiomyocyte survival by easing the autophagic flux blocked by DOX. In addition, rapamycin reduced oxidative stress, prevented mitochondrial damage, and restored energy metabolic homeostasis in DOX-treated cardiomyocytes. In vivo, we used metformin (Met) which is an AMPK activator to protect cardiac tissue to alleviate DOX-induced dilated cardiomyopathy. In this study, Met significantly attenuated the oxidative stress response of myocardial tissue caused by DOX and activated cardiomyocyte autophagy to maintain cardiomyocyte energy metabolism and reduce cardiomyocyte apoptosis by downregulating mTOR activity. Overall, our study revealed the role of autophagy and apoptosis in DOX-induced dilated cardiomyopathy and demonstrated the potential role of regulation of the AMPK/mTOR axis in the treatment of DOX-induced dilated cardiomyopathy.

Aurantiamide Acetate Ameliorates Lung Inflammation in Lipopolysaccharide-Induced Acute Lung Injury in Mice.

Purpose: Aurantiamide acetate (AA) is a dipeptide derivative with complex pharmacological activities and remarkable effects on preventing and treating various diseases. In the current study, we aimed to investigate whether AA can exert protective effects in a mouse model of ALI induced by LPS. Materials and Methods: In this model, mice were given intranasal LPS for 3 days prior to receiving AA (2.5, 5, and 10 mg/kg) via oral gavage. An assessment of histopathological changes was performed by hematoxylin and eosin (HE). Proinflammatory cytokines were detected in bronchoalveolar lavage fluids (BALFs) by enzyme-linked immunosorbent assays (ELISAs). The effects of AA on protein expression of NF-κB and PI3K/AKT signaling pathways were determined by Western blot. In addition, lung wet/dry (W/D) weight ratio, myeloperoxidase (MPO) activity, cell counts, and protein content were also measured. Results: According to results, AA pretreatment significantly reduced lung pathological changes, W/D ratio, MPO activity, and protein content. Additionally, AA resulted in a significant reduction in the number of total cells, neutrophils, and proinflammatory cytokines in the BALF after LPS stimulation. The subsequent study revealed that pretreatment with AA dose dependently suppressed LPS-induced activation of NF-κB as well as PI3K/AKT phosphorylation. Conclusion: The results indicated that the AA had a protective effect on LPS-induced ALI in mice and could be a potential drug for ALI.

Refined polysaccharide from Dendrobium devonianum resists H1N1 influenza viral infection in mice by activating immunity through the TLR4/MyD88/NF-κB pathway.

Dendrobium polysaccharide exhibits multiple biological activities, such as immune regulation, antioxidation, and antitumor. However, its resistance to viral infection by stimulating immunity is rarely reported. In this study, we explored the effect and mechanism of DVP-1, a novel polysaccharide from Dendrobium devonianum, in the activation of immunity. After being activated by DVP-1, the ability of mice to prevent H1N1 influenza virus infection was investigated. Results of immune regulation showed that DVP-1 significantly improved the immune organ index, lymphocyte proliferation, and mRNA expression level of cytokines, such as IL-1ß, IL-4, IL-6, and TNF-α in the spleen. Immunohistochemical results showed that DVP-1 obviously promoted the mucosal immunity in the jejunum tissue. In addition, the expression levels of TLR4, MyD88, and TRAF6 and the phosphorylation levels of TAK1, Erk, JNK, and NF-κB in the spleen were upregulated by DVP-1. The virus infection results showed that the weight loss of mice slowed down, the survival rate increased, the organ index of the lung reduced, and the virus content in the lung decreased after DVP-1 activated immunity. By activating immunity with DVP-1, the production of inflammatory cells and inflammatory factors in BALF, and alveolar as well as peribronchiolar inflammation could be prevented. The results manifested that DVP-1 could resist H1N1 influenza virus infection by activating immunity through the TLR4/MyD88/NF-κB pathway.

CHMP1A suppresses the growth of renal cell carcinoma cells via regulation of the PI3K/mTOR/p53 signaling pathway.

BACKGROUND: CHMP1A, a member of the ESCRT-III complex family, has been indicated as a brand-new inhibitor gene of tumors. Our previous research has revealed that CHMP1A plays a vital role in the development and progression of renal cell carcinoma (RCC). OBJECTIVE: To investigate the potential target pathway of the regulation of the tumor cell growth by CHMP1A. METHODS: The effect of CHMP1A on mTOR pathway was elucidated by western blotting. The effect of CHMP1A on the expression of p53 was evaluated, and A498 cell growth was assessed by colony formation and MTT assays. The expression of p53 was knocked down by shRNA-p53, and the effect of CHMP1A on mTOR after knockdown of p53 was evaluated. The effect of CHMP1A on apoptosis and its relationship with MDM2 pathway were detected by western blotting and FCM. Finally, the relationship between the regulation of p53 by CHMP1A and the PI3K/mTOR pathway was detected. RESULTS: This study showed that the mTOR pathway was suppressed significantly in CHMP1A-overexpressing A498 and 786-0 cells; moreover, the enhanced expression of p53 and the reduced proliferation were shown in CHMP1A-overexpressing A498 cells. Furthermore, CHMP1A was able to regulate the PI3K/PTEN/mTOR and MDM2/p53 pathways in order to suppress RCC. In addition, CHMP1A regulated Bax and Bcl-2 via MDM2/p53 to induce the apoptosis of tumor cells and upregulated the expression of p53 via the PI3K/mTOR pathway. CONCLUSIONS: The results convey that CHMP1A-related suppression of RCC is closely related to the PI3K/mTOR/p53 pathway.

Herbal Active Ingredients: Potential for the Prevention and Treatment of Acute Lung Injury.

Acute lung injury (ALI) is a life-threatening clinical syndrome with high morbidity and mortality. The main pathological features of ALI are increased alveolar-capillary membrane permeability, edema, uncontrolled migration of neutrophils to the lungs, and diffuse alveolar damage, resulting in acute hypoxemic respiratory failure. Glucocorticoids, aspirin, and other anti-inflammatory drugs are commonly used to treat ALI. Respiratory supports, such as a ventilator, are used to alleviate hypoxemia. Many treatment methods are available, but they cannot significantly ameliorate the quality of life of patients with ALI and reduce mortality rates. Herbal active ingredients, such as flavonoids, terpenoids, saponins, alkaloids, and quinonoids, exhibit advantages for ALI prevention and treatment, but the underlying mechanism needs further study. This paper summarizes the role of herbal active ingredients in anti-ALI therapy and progresses in the understanding of their mechanisms. The work also provides some references and insights for the discovery and development of novel drugs for ALI prevention and treatment.

Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice.

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

A novel polysaccharide from Dendrobium devonianum serves as a TLR4 agonist for activating macrophages.

Dendrobium devonianum has been used as herbal medicines and nutraceutical products since ancient time in China. However, its chemical composition and pharmacological mechanisms are not fully known. In present studies, by chemical purification and characteristic identification, we discovered a novel polysaccharide from D. devonianum, which was designated as DvP-1 with molecular weights of 9.52 × 104 Da. DvP-1 is a homogeneous heteropolysaccharide consisting of D-mannose and d-glucose in the molar ration of 10.11: 1. The main glycosidic linkages were ß-1, 4-Manp, which were substituted with acetyl groups at the O-2, O-3 and/or O-6 positions. DvP-1 was found to directly stimulate the activation of macrophages in vitro, as evidenced by inducing morphologic change, thereby promoting the production of cytokines TNF-α, IL-6 and NO, and enhancing the pinocytic activity of macrophages. By establishing a zebrafish model, we also found that DvP-1 could alleviate vinorelbine-induced decrease of macrophages in vivo. Further findings indicated that DvP-1 activated macrophages through several toll-like receptors (TLRs), but mainly through TLR4. DvP-1 served as a TLR4 agonist and induced ERK, JNK, p38, and IκB-α phosphorylation, suggesting the activation of MAPK and NFκB signaling pathways downstream of TLR4. These findings could help us further understand the immunomodulating effects of D. devonianum in Chinese medicines or health foods for immunocompromised persons. They also show the medicinal value of DvP-1 for the treatment of cancer and infectious diseases caused by TLR4 dysfunction.

Salidroside Protects Lipopolysaccharide-Induced Acute Lung Injury in Mice.

Salidroside (SDS) has been reported to have anti-inflammatory properties. The objective of this study was to investigate the protective effect of SDS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with SDS 1 hour before intranasal instillation of LPS. Seven hours after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of pro-inflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1ß (IL 1ß), and IL-6 in the BALF were measured by enzyme-linked immunosorbent assay. The expression of Toll-like receptor 4 (TLR4), inhibitor of nuclear factor-kappa B (IκB-α), and nuclear factor-kappa B (NF-κB) p65 was detected by Western blot. The SDS reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs, attenuated the LPS-induced histological alterations in the lung, and inhibited the production of TNF-α, IL-1ß, and IL-6. Western blot showed that SDS efficiently inhibited the phosphorylation of IκB-α, p65 NF-κB, and the expression of TLR4. These data show that the anti-inflammatory effects of SDS (at least 20 mg/kg) against LPS-induced ALI due to its ability to inhibit TLR4 mediated the NF-κB signaling pathways. The SDS may represent a novel strategy for treating LPS-induced ALI.

Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity.

The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy.