Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

INTRODUCTION: Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. OBJECTIVE: This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. METHOD: Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. RESULTS: We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. CONCLUSIONS: The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

Study and analysis of the correlation between lumbar spondylolisthesis and Modic changes.

Background: This study aimed to explore the risk factors of Modic changes in lumbar spondylolisthesis. Methods: The distribution of Modic changes in different types of lumbar spondylolisthesis, degree of spondylolisthesis, and degree of intervertebral disc degeneration in patients with lumbar spondylolisthesis was observed and analyzed. Statistical analysis was conducted to assess whether intervertebral disc degeneration, local mechanical changes, etc. affect the occurrence of Modic changes. The risk factors of Modic changes in lumbar spondylolisthesis were further illustrated. Results: The age in the lumbar spondylolisthesis with Modic changes group was younger than that in the lumbar spondylolisthesis without Modic changes group, and the bone mineral density was better in the lumbar spondylolisthesis with Modic changes group than that in the lumbar spondylolisthesis without Modic changes group, P < 0.05. The two groups statistically differed in intervertebral disc height (IDH) and disc angle on magnetic resonance imaging (MRI). In the classification of Modic changes, the incidence of type II was the highest. The incidence of Modic changes is higher in isthmic spondylolisthesis than in degenerative spondylolisthesis. With the aggravation of lumbar spondylolisthesis and intervertebral disc degeneration, the incidence of Modic changes gradually increased. Modic changes are most commonly seen in both the upper and lower endplates. Logistic regression analysis showed that the occurrence of Modic changes in lumbar spondylolisthesis was significantly correlated with IDH, disc angle on MRI, type of spondylolisthesis, degree of spondylolisthesis, and degree of intervertebral disc degeneration, P < 0.05. Conclusions: The occurrence of Modic changes is related to the type of spondylolisthesis, the degree of spondylolisthesis, the degree of disc degeneration, the decrease of intervertebral disc height, and local stress angulation.

Relationship among screen time，depressive symptoms and sleep parameters among college students / 中国学校卫生

Objective@#To explore the relationship between daytime or nighttime screen time, sleep duration, bedtime, sleep quality and depressive symptoms, so as to provide reference for preventing depression symptoms in college students.@*Methods@#A total of 1 259 college students in one university in Beijing were recruited by using a cluster random sampling method for online and offline questionnaire surveys in October 2022 and April to May 2023. The sleeping quality, depression symptoms and screen time of participants were measured with the Pittsburgh Sleep Quality Index(PSQI), Chinese Version of the Beck Depression Inventory-II (BDI-II-C) and Screen Time Questionnaire. Logistic ordered regression and multiple linear regression were used to analyze the correlation among screen time, sleep parameters and depressive symptoms.@*Results@#The prevalence of depressive symptoms was 24.9 %. There was no significant correlation between daytime screen time and depressive symptoms for a week after controlling for night screen time in a week, gender and age ( OR= 1.00 , 95%CI=1.00-1.01, P >0.05). There was a significant correlation between night screen time and depressive symptoms for a week ( OR=1.05, 95%CI=1.03-1.06, P <0.01) after controlling for daytime screen time in a week, gender and age. However, after controlling for the weekday sleep duration, weekend bedtime, and sleep quality step by step, there was no significant correlation between the night screen time for a week and the depressive symptoms ( OR=1.01, 95%CI= 0.99 -1.02, P >0.05). After adjusting for gender and age, multiple linear regression analysis found that the duration of one week s night vision screen had statistical significance in predicting weekday sleep duration, weekend sleep time and sleep quality ( β=-0.29, 0.45, 0.26, P <0.05). There were positive correlation between the duration of sleep on study days, the duration of sleep on rest days, and the quality of sleep with depressive symptoms（ OR =1.27,1.39,1.45， P <0.01）.@*Conclusions@#Excessive night screen time has a greater impact on sleep problems and depressive symptoms. Reducing nighttime video and improving sleep habits are potential intervention goals for reducing depression symptoms in college students.

Pi-Pa-Run-Fei-Tang alleviates lung injury by modulating IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB signaling pathway and balancing Th17 and Treg in murine model of OVA-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. AIM OF THE STUDY: The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. MATERIALS AND METHODS: A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1ß, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO, NO, SOD, GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. RESULTS: PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation, and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1ß, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine, and threonine metabolism. CONCLUSION: This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.

Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection.

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.

Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis / 中国中药杂志

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Screening immune adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae.

In this study, we screened adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae (E. rhusiopathiae). Inactivated cells of E. rhusiopathiae strain HG-1 were prepared as the antigen in five adjuvanted inactivated vaccines, including a mineral-oil-adjuvanted vaccine (Oli vaccine), aluminum-hydroxide-gel-adjuvanted vaccine (Alh vaccine), ISA201-biphasic-oil-emulsion-adjuvanted vaccine (ISA201 vaccine), GEL02-water-soluble-polymer-adjuvanted vaccine (GEL vaccine), and IMS1313-water-soluble-nanoparticle-adjuvanted vaccine (IMS1313 vaccine). The safety test results of subcutaneous inoculation in mice showed that Oli vaccine had the most severe side effects, with a combined score of 35, followed by the ISA201 vaccine (25 points), Alh vaccine (20 points), GEL vaccine (10 points), and IMS1313 vaccine (10 points). A dose of 1.5LD50 of strain HG-1 was used to challenge the mice intraperitoneally, 14 days after their second immunization. The protective efficacy of Oli vaccine and Alh vaccine was 100% (8/8), whereas that of the other three adjuvanted vaccines was 88% (7/8). Challenge with 2.5LD50 of strain HG-1 resulted in a 100% survival rate, demonstrating the 100% protective efficacy of the Oli vaccine, followed by the GEL vaccine (71%, 5/7), IMS1313 vaccine (57%, 4/7), ISA201 vaccine (43%, 3/7), and Alh vaccine (29%, 2/7). Challenge with 4LD50 of strain HG-1 showed 100% (7/7) protective efficacy of the Oli vaccine and 71% (5/7) protective efficacy of the GEL vaccine, whereas the protective efficacy of other three adjuvanted vaccine was 14% (1/7). The Alh and GEL vaccines were selected for comparative tests in piglets, and both caused minor side effects. A second immunization with these two adjuvanted vaccines conferred 60 and 100% protective efficacy, respectively, after the piglets were challenged via an ear vein with 8LD100 of strain HG-1. After challenge with 16LD100 of strain HG-1, the Alh and GEL vaccines showed 40% and 100% protective efficacy, respectively. Our results suggested that GEL is the optimal adjuvant for an inactivated vaccine against E. rhusiopathiae.

MicroRNAs and other small RNAs in Aedes aegypti saliva and salivary glands following chikungunya virus infection.

Mosquito saliva facilitates blood feeding through the anti-haemostatic, anti-inflammatory and immunomodulatory properties of its proteins. However, the potential contribution of non-coding RNAs to host manipulation is still poorly understood. We analysed small RNAs from Aedes aegypti saliva and salivary glands and show here that chikungunya virus-infection triggers both the siRNA and piRNA antiviral pathways with limited effects on miRNA expression profiles. Saliva appears enriched in specific miRNA subsets and its miRNA content is well conserved among mosquitoes and ticks, clearly pointing to a non-random sorting and occurrence. Finally, we provide evidence that miRNAs from Ae. aegypti saliva may target human immune and inflammatory pathways, as indicated by prediction analysis and searching for experimentally validated targets of identical human miRNAs. Overall, we believe these observations convincingly support a scenario where both proteins and miRNAs from mosquito saliva are injected into vertebrates during blood feeding and contribute to the complex vector-host-pathogen interactions.

Isolated Mycotic Internal Iliac Artery Aneurysm Treated With a Combined Endovascular Stenting and Percutaneous Drainage Approach: A Case Report and Review of Current Literature.

BACKGROUND: Isolated mycotic internal iliac artery aneurysms are rare and management of these patients can be complex. CASE SUMMARY: We present a rare case of isolated mycotic right internal iliac artery aneurysm caused by Salmonella enteritides. This was managed in stages - with intravenous antibiotics, followed by endovascular stenting and embolization, and subsequent percutaneous drainage of the remnant collection. The patient had no perioperative complications, and has remained well at more than 18 months post-operatively with no evidence of stent infection. CONCLUSION: A minimally-invasive approach combining endovascular aneurysm repair and percutaneous drainage is a viable option in the management of a mycotic internal iliac artery aneurysm.

Aedes mosquitoes in the emerging threat of urban yellow fever transmission.

This last decade has seen a resurgence of yellow fever (YF) in historical endemic regions and repeated attempts of YF introduction in YF-free countries such as the Asia-Pacific region and the Caribbean. Infected travellers are the main entry routes in these regions where competent mosquito vectors proliferate in appropriate environmental conditions. With the discovery of the 17D vaccine, it was thought that YF would be eradicated. Unfortunately, it was not the case and, contrary to dengue, chikungunya and Zika, factors that cotribute to YF transmission remain under investigation. Today, all the signals are red and it is very likely that YF will be the next pandemic in the YF-free regions where millions of people are immunologically naïve. Unlike COVID-19, YF is associated with a high case-fatality rate and a high number of deaths are expected. This review gives an overview of global YF situation, including the non-endemic Asia-Pacific region and the Caribbean where Aedes aegypti is abundantly distributed, and also proposes different hypotheses on why YF outbreaks have not yet occurred despite high records of travellers importing YF into these regions and what role Aedes mosquitoes play in the emergence of urban YF.

Study on the improvement of quality standard for Niushanggui capsules / 中国药房

OBJECT IVE To provide reference for the improvement of the quality standard for Niushanggui capsules. METHODS Based on the previous quality standard ，thin-layer chromatography （TLC）identification methods were established for Angelicae dahurica and Anemarrhenae asphodeloides . High performance liquid chromatography （HPLC）method was established to determine the contents of 5 components simultaneously ，such as mangiferin ，prim-O-glucosylcimifugin，naringin，neohesperidin and 5-O-methylvisammioside. The limits were confirmed. RESULTS TLC chromatogram of Niushanggui capsules showed the same color spots in the same position as the corresponding （mixed）substance control or reference medicinal material of A. dahuricae and A. asphodeloides ，while the negative samples had no interference. The linear range of mangiferin ，prim-O-glucosylcimifugin， naringin，neohesperidin and 5-O-methylvisammioside were 7.98-127.63，6.74-107.84，53.06-848.96，39.31-628.90，13.54-216.62 μg/mL，respectively（all r＝0.999 9）. RSDs of precision ，stability（24 h）and repeatability tests were all no more than 1.20％（n＝ 6）. The average recoveries were 95.00％，105.16％，97.16％，101.00％ and 104.97％（RSD≤1.50％，n＝6）. In 4 batches of samples，the average contents of the above 5 components were 0.842，0.696，6.951，5.755 and 1.106 mg/g respectively ；the limits of A. asphodeloides ，Saposhnikovia divaricata and Citrus aurantium were based on the contents of mangiferin ，the total content of prim-O-glucosylcimmifugin and 5-O-methylvisammioside，naringin and neohesperidin ，which would not be less than 0.42，0.90 and 6.36 mg/grain，respectively. CONCLUSIONS TLC identification methods of A. dahurica and A. asphodeloides and the content determination methods of 5 components as mangiferin in Niushanggui capsules are established in this study ，and the limits of A. asphodeloides ，S. divaricata and C. aurantium are confirmed.

Transgenic refractory Aedes aegypti lines are resistant to multiple serotypes of dengue virus.

The areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread of Aedes species, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito's salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans. Here we used the mariner Mos1 transposase to create an Aedes aegypti line that expresses virus-specific miRNA hairpins capable of blocking DENV replication. These microRNA are driven by the blood-meal-inducible carboxypeptidase A promoter or by the polyubiquitin promoter. The transgenic mosquitoes exhibited significantly lower infection rates and viral titers for most DENV serotypes 7 days after receiving an infectious blood meal. The treatment was also effective at day 14 post infection after a second blood meal had been administered. In viral transmission assay, we found there was significantly reduced transmission in these lines. These transgenic mosquitoes were effective in silencing most of the DENV genome; such an approach may be employed to control a dengue fever epidemic.

Celastrol in cancer therapy: Recent developments, challenges and prospects.

Cancer is one of the world's biggest healthcare burdens and despite the current advancements made in treatment plans, the outcomes for oncology patients have yet to reach their full potential. Hence, there is a pressing need to develop novel anti-cancer drugs. A popular drug class for research are natural compounds, due to their multi-targeting potential and enhanced safety profile. One such promising natural bioactive compound derived from a vine, Tripterygium wilfordii is celastrol. Pre-clinical studies revolving around the use of celastrol have revealed positive pharmacological activities in various types of cancers, thus suggesting the chemical's potential anti-cancerous effects. However, despite the numerous preclinical studies carried out over the past few decades, celastrol has not reached human trials for cancer. In this review, we summarize the mechanisms and therapeutic potentials of celastrol in treatment for different types of cancer. Subsequently, we also explore the possible reasons hindering its development for human use as cancer therapy, like its narrow therapeutic window and poor pharmacokinetic properties. Additionally, after critically analysing both in vitro and in vivo evidence, we discuss about the key pathways effected by celastrol and the suitable types of cancer that can be targeted by the natural drug, thus giving insight into future directions that can be taken, such as in-depth analysis and research of the druggability of celastrol derivatives, to aid the clinical translation of this promising anti-cancer lead compound.

Lipopolysaccharides Enhance Epithelial Hyperplasia and Tubular Adenoma in Intestine-Specific Expression of krasV12 in Transgenic Zebrafish.

Intestinal carcinogenesis is a multistep process that begins with epithelial hyperplasia, followed by a transition to an adenoma and then to a carcinoma. Many etiological factors, including KRAS mutations and inflammation, have been implicated in oncogenesis. However, the potential synergistic effects between KRAS mutations and inflammation as well as the potential mechanisms by which they promote intestinal carcinogenesis remain unclear. Thus, the objective of this study was to investigate the synergistic effects of krasV12, lipopolysaccharides (LPS), and/or dextran sulfate sodium (DSS) on inflammation, tumor progression, and intestinal disorders using transgenic adults and larvae of zebrafish. Histopathology and pathological staining were used to examine the intestines of krasV12 transgenic zebrafish treated with LPS and/or DSS. LPS and/or DSS treatment enhanced intestinal inflammation in krasV12 transgenic larvae with concomitant increases in the number of neutrophils and macrophages in the intestines. The expression of krasV12, combined with LPS treatment, also enhanced epithelial hyperplasia and tubular adenoma, demonstrated by histopathological examinations and by increases in cell apoptosis, cell proliferation, and downstream signaling of phosphorylated AKT serine/threonine kinase 1 (AKT), extracellular-signal-regulated kinase (ERK), and histone. We also found that krasV12 expression, combined with LPS treatment, significantly enhanced changes in intestinal morphology, specifically (1) decreases in goblet cell number, goblet cell size, villi height, and intervilli space, as well as (2) increases in villi width and smooth muscle thickness. Moreover, krasV12 transgenic larvae cotreated with DSS and LPS exhibited exacerbated intestinal inflammation. Cotreatment with DSS and LPS in krasV12-expressing transgenic adult zebrafish also enhanced epithelial hyperplasia and tubular adenoma, compared with wild-type fish that received the same cotreatment. In conclusion, our data suggest that krasV12 expression, combined with LPS and/or DSS treatment, can enhance intestinal tumor progression by activating the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway and may provide a valuable in vivo platform to investigate tumor initiation and antitumor drugs for gastrointestinal cancers.

Exercise-Induced Rhabdomyolysis: A Case Series of Spin-Related Rhabdomyolysis.

Exercise rhabdomyolysis is a potentially life-threatening medical condition if not adequately managed early. With the increase in the popularity of indoor cycling, known as Spinning®, over recent years, there has been an increased occurrence of spin-related rhabdomyolysis observed among previously fit adults after undertaking their first spin bike class session. They present with the triad of myalgia, muscle weakness, and dark tea-colored urine within a week of their first spin session. This case series highlights several admissions to the hospital with spin-related rhabdomyolysis and their clinical management.

Resveratrol for cancer therapy: Challenges and future perspectives.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been expected to ameliorate cancer and foster breakthroughs in cancer therapy. Despite thousands of preclinical studies on the anticancer activity of resveratrol, little progress has been made in translational research and clinical trials. Most studies have focused on its anticancer effects, cellular mechanisms, and signal transduction pathways in vitro and in vivo. In this review, we aimed to discern the causes that prevent resveratrol from being used in cancer treatment. Among the various limitations, poor pharmacokinetics and low potency seem to be the two main bottlenecks of resveratrol. In addition, resveratrol-induced nephrotoxicity in multiple myeloma patients hinders its further development as an anticancer drug. New insights and strategies have been proposed to accelerate the conversion of resveratrol from bench to bedside. In the interim, the most promising approach is to enhance the bioavailability of resveratrol with new formulations. Alternatively, more potent analogues of resveratrol could be developed to augment its anticancer potency. Given all the gaps mentioned, much work remains to be done. However, if remarkable progress can be made, resveratrol may finally be used for cancer therapy.

Evaluation of the Implementation and Effectiveness of Community-Based Brain-Computer Interface Cognitive Group Training in Healthy Community-Dwelling Older Adults: Randomized Controlled Implementation Trial.

BACKGROUND: Cognitive training can improve cognition in healthy older adults. OBJECTIVE: The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. METHODS: A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). RESULTS: A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased (b=2.32, P=.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated (b=-0.57, P=.01, 95% CI [-1.00 to -0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 (b=-13.5, P=.01, 95% CI [-23.95 to -3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group (b=5.38, P=.06, 95% CI [-0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest (b=-0.36, P=.08, 95% CI [-0.75 to 0.04]) and visuospatial domain (b=0.46, P=.08, 95% CI [-0.05 to 0.96]) that were not statistically significant. CONCLUSIONS: CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04439591; https://clinicaltrials.gov/ct2/show/NCT04439591.

[Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis].

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) µg·L~(-1),(1 121.34±91.65) µg·L~(-1) and(2 951.91±360.53) µg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-ß1(TGF-ß1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.