Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

The role of tumor parenchyma and brain cortex signal intensity ratio in differentiating solitary fibrous tumors and meningiomas.

BACKGROUND: Solitary fibrous tumors (SFT) and meningiomas (MA) have similar clinical and radiographic presentations but require different treatment approaches and have different prognoses. This emphasizes the importance of a correct preoperative diagnosis of SFT versus MA. OBJECTIVE: In this study, investigated the differences in imaging characteristics between SFT and MA to improve the accuracy of preoperative imaging diagnosis of SFT. METHODS: The clinical and imaging data of 26 patients with SFT and 104 patients with MA who were pathologically diagnosed between August 2017 and December 2022, were retrospectively analyzed. The clinical and imaging differences between SFT and MA, as well as between the various pathological grades of SFT, were analyzed. RESULTS: Age, gender, cystic change, flow void phenomenon, yin-yang sign, lobulation, narrow base, tumor/cortex signal ratio (TCSR) > 1.0 in T1-weighted imaging (T1WI), TCSR ≥ 1.1 in T2-weighted imaging (T2WI), peritumoral edema, and absence of dural tail sign varied between SFT and MA. As per the receiver operating characteristic (ROC) curve analysis, TCSR > 1 in T1WI has the maximum diagnostic accuracy for SFT. Cranial or venous sinus invasion had a positive effect on SFT (Grade III, World Health Organization (WHO) grading). CONCLUSION: Among the many radiological and clinical distinctions between SFT and MA, TCSR ≥ 1 exhibits the highest predictive efficacy for SFT; while cranial or venous sinus invasion may be a predictor of WHO grade III SFT.

Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3.

Hesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis-related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing.

Different Acupuncture Therapies for Postherpetic Neuralgia: An Overview of Systematic Reviews and Meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).

Enhanced indigenous consortia for the remediation of uranium-contaminated groundwater by bioaugmentation: Reducing and phosphate-solubilizing consortia.

To investigate the strengthening effects and mechanisms of bioaugmentation on the microbial remediation of uranium-contaminated groundwater via bioreduction coupled to biomineralization, two exogenous microbial consortia with reducing and phosphate-solubilizing functions were screened and added to uranium-contaminated groundwater as the experimental groups (group B, reducing consortium added; group C, phosphate-solubilizing consortium added). ß-glycerophosphate (GP) was selected to stimulate the microbial community as the sole electron donor and phosphorus source. The results showed that bioaugmentation accelerated the consumption of GP and the proliferation of key functional microbes in groups B and C. In group B, Dysgonomonas, Clostridium_sensu_stricto_11 and Clostridium_sensu_stricto_13 were the main reducing bacteria, and Paenibacillus was the main phosphate-solubilizing bacteria. In group C, the microorganisms that solubilized phosphate were mainly unclassified_f_Enterobacteriaceae. Additionally, bioaugmentation promoted the formation of unattached precipitates and alleviated the inhibitory effect of cell surface precipitation on microbial metabolism. As a result, the formation rate of U-phosphate precipitates and the removal rates of aqueous U(VI) in both groups B and C were elevated significantly after bioaugmentation. The U(VI) removal rate was poor in the control group (group A, with only an indigenous consortium). Propionispora, Sporomusa and Clostridium_sensu_stricto_11 may have played an important role in the removal of uranium in group A. Furthermore, the addition of a reducing consortium promoted the reduction of U(VI) to U(IV), and immobilized uranium existed in the form of U(IV)-phosphate and U(VI)-phosphate precipitates in group B. In contrast, U was present mainly as U(VI)-phosphate precipitates in groups A and C. Overall, bioaugmentation with an exogenous consortium resulted in the rapid removal of uranium from groundwater and the formation of U-phosphate minerals and served as an effective strategy for improving the treatment of uranium-contaminated groundwater in situ.

Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis.

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.

Mapa de evidências sobre a efetividade clínica da acupuntura: informe executivo. / Evidence map on clinical effectiveness of acupuncture: executive report

Este informe executivo apresenta os principais achados do mapa de evidências sobre os efeitos da Acupuntura para desfechos em saúde, que representa a evidência de 163 estudos de revisão que analisaram o efeito da acupuntura como intervenção para pelo menos um dos 96 desfechos de saúde organizados em 14 grupos: Câncer e Neoplasias; Dor; Doenças Cardiovasculares; Doenças Respiratórias; Doenças Reumáticas e Musculoesqueléticas; Doenças Nutricionais, Metabólicas e Endócrinas; Doenças do Sistema Nervoso; Dermatopatias; Gastroenteropatias; Indicadores Metabólicos e Fisiológicos; Oftalmopatias e Otorrinolaringopatias; Sinais e Sintomas; Transtornos Mentais; e Outros desfechos. No todo foram 201 associações entre acupuntura e os desfechos de saúde. Para cada associação intervenção-desfecho foi incluído o efeito reportado pelo estudo de revisão.

This executive report presents the main findings of the evidence map on the effects of acupuncture for health outcomes, representing evidence from 163 review studies that analyzed the effect of acupuncture as an intervention for at least one of the 96 health outcomes organized into 14 groups: Cancer and Neoplasms; Pain; Cardiovascular Diseases; Respiratory Diseases; Rheumatic and Musculoskeletal Diseases; Nutritional, Metabolic, and Endocrine Diseases; Diseases of the Nervous System; Dermatopathies; Gastroenteropathies; Metabolic and Physiological Indicators; Ophthalmopathies and Otorhinolaryngopathies; Signs and Symptoms; Mental Disorders; and Other outcomes. In total, there were 201 associations between acupuncture and health outcomes. For each intervention-outcome association, the reported effect by the review study was included.

Este informe ejecutivo presenta los principales hallazgos del mapa de evidencia sobre los efectos de la acupuntura en los resultados de salud, representando la evidencia de 163 estudios de revisión que analizaron el efecto de la acupuntura como intervención para al menos uno de los 96 resultados de salud organizados en 14 grupos: Cáncer y Neoplasias; Dolor; Enfermedades Cardiovasculares; Enfermedades Respiratorias; Enfermedades Reumáticas y Musculoesqueléticas; Enfermedades Nutricionales, Metabólicas y Endocrinas; Enfermedades del Sistema Nervioso; Dermatopatías; Gastroenteropatías; Indicadores Metabólicos y Fisiológicos; Oftalmopatías y Otorrinolaringopatías; Signos y Síntomas; Trastornos Mentales; y Otros resultados. En total, hubo 201 asociaciones entre la acupuntura y los resultados de salud. Para cada asociación intervención-resultados se incluyó el efecto informado por el estudio de revisión.

Maleic acid and malonic acid reduced the pathogenicity of Sclerotinia sclerotiorum by inhibiting mycelial growth, sclerotia formation and virulence factors.

Sclerotinia sclerotiorum is a necrotrophic plant pathogenic fungus with broad distribution and host range. Bioactive compounds derived from plant extracts have been proven to be effective in controlling S. sclerotiorum. In this study, the mycelial growth of S. sclerotiorum was effectively inhibited by maleic acid, malonic acid, and their combination at a concentration of 2 mg/mL, with respective inhibition rates of 32.5%, 9.98%, and 67.6%. The treatment of detached leaves with the two acids resulted in a decrease in lesion diameters. Interestingly, maleic acid and malonic acid decreased the number of sclerotia while simultaneously increasing their weight. The two acids also disrupted the cell structure of sclerotia, leading to sheet-like electron-thin regions. On a molecular level, maleic acid reduced oxalic acid secretion, upregulated the expression of Ss-Odc2 and downregulated CWDE10, Ss-Bi1 and Ss-Ggt1. Differently, malonic acid downregulated CWDE2 and Ss-Odc1. These findings verified that maleic acid and malonic acid could effectively inhibit S. sclerotiorum, providing promising evidence for the development of an environmentally friendly biocontrol agent.

Study on the mechanism of action of effective monomeric, berberine of Xianglian Pill in inhibiting human colon cancer cells based on fatty acid synthase target.

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

[Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification].

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1ß(IL-1ß). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1ß, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management.

BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Neural control of cerebral blood flow: scientific basis of scalp acupuncture in treating brain diseases.

Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase.

OBJECTIVE: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. METHODS: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg-1•d-1), MPA + low-dose (20 mg•kg-1•d-1) JP (L-JP), MPA + medium-dose (30 mg•kg-1•d-1) JP (M-JP), and MPA + high-dose (40 mg•kg-1•d-1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. RESULTS: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. CONCLUSIONS: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aß generation.

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.

Steroidal constituents from Solanum nigrum.

Three previously undescribed steroidal constituents including two sterols (1-2) and one pregnane-type steroidal glycoside (6), along with nineteen known ones (3-5, 7-22), were isolated from the 80% alcohol extraction of Solanum nigrum L. Their structures and the absolute configurations were established by analysis of the extensive spectroscopic data (1H/13 NMR, 1H1H COSY, HSQC, HMBC, and NOESY), and/or by comparisons of the experimental electronic circular dichroism (ECD) spectra with those calculated ones by TDDFT method. Further, a MTT assay was applied to demonstrate that compounds 1-4, 6-12, 18, and 22 exhibited significant cytotoxic activities against SW480 cells, and compounds 1-4, 6-14, and 16-22 showed significant cytotoxic activities against Hep3B cells.

Application potential of Humulus Scandens in livestock husbandry.

On the background of antibiotic-free livestock husbandry, animal nutritionists are trying to find alternatives to antibiotics. Many herbs have been developed for animal diets to replace antibiotics. Humulus Scandens (HS) is also known as Humulus japonicus and Japanese hop in English, lü Cao () in Mandarin Chinese and kanamugura (カナムグラ) in Japanese. It is a traditional Chinese medicine with good environmental adaptability. It can grow rapidly and cover any area. Its high yield, strong vitality and medical value allow its potential to be used as an exogenous additive for animal diets to replace antibiotics. However, the knowledge about this herb is limited at present. This manuscript reviewed the processing method of HS and its application in livestock husbandry in order to provide references for its application.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice.

Neurons in the lateral hypothalamus expressing the neuropeptide Hypocretin, also known as orexin, are known critical modulators of arousal stability. However, their role in the different components of the arousal construct such as attention and decision making is poorly understood. Here we study Hypocretin neuronal circuit dynamics during stop action impulsivity in a Go/NoGo task in mice. We show that Hypocretin neuronal activity correlates with anticipation of reward. We then assessed the causal role of Hypocretin neuronal activity using optogenetics in a Go/NoGo task. We show that stimulation of Hypocretin neurons during the cue period dramatically increases the number of premature responses. These effects are mimicked by amphetamine, reduced by atomoxetine, a norepinephrine uptake inhibitor, and blocked by a Hypocretin receptor 1 selective antagonist. We conclude that Hypocretin neurons have a key role in the integration of salient stimuli during wakefulness to produce appropriate and timely responses to rewarding and aversive cues.

Antinociceptive C19-diterpenoid alkaloids from the roots of Aconitum nagarum.

Three new C19-diterpenoid alkaloids, nagarumines A-C (1-3), together two known alkaloids, deoxyaconitine (4) and N-deethyldeoxyaconitine (5), were isolated from the roots of Aconitum nagarum. The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as high resolution mass spectrometry. The in vivo pharmacological studies revealed that nagarumine C (3) possessed comparable antinociceptive activity (ED50 = 76.0 µmol/kg) with the positive control drugs aspirin and acetaminophen.