Targeting RhoA expression with formononetin and salvianolic acid B to mitigate pancreatic cancer-associated endothelial cells changes.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of Qi and blood in Traditional Chinese Medicine (TCM), the combination of Qi-reinforcing herbs and blood-activating herbs has a synergistic effect in improving blood stasis syndrome, especially in tumor treatment. The classic "Radix Astragali - Salvia miltiorrhiza" duo exemplifies this principle, renowned for invigorating Qi and activating blood flow, employed widely in tumor therapies. Our prior research underscores the potent inhibition of pancreatic tumor xenografts by the combination of Formononetin (from Radix Astragali) and Salvianolic acid B (from Salvia miltiorrhiza) in vitro. However, it remains unclear whether this combination can inhibit the abnormal vascularization of pancreatic tumors to achieve its anti-cancer effect. AIM OF THE STUDY: Abnormal vasculature, known to facilitate tumor growth and metastasis. Strategies to normalize tumor-associated blood vessels provide a promising avenue for anti-tumor therapy. This study aimed to unravel the therapeutic potential of Formononetin combined with Salvianolic acid B (FcS) in modulating pancreatic cancer's impact on endothelial cells, illuminate the underlying mechanisms that govern this therapeutic interaction, thereby advancing strategies to normalize tumor vasculature and combat cancer progression. MATERIALS AND METHODS: A co-culture system involving Human Umbilical Vein Endothelial Cells (HUVECs) and PANC-1 cells was established to investigate the potential of targeting abnormal vasculature as a novel anti-tumor therapeutic strategy. We systematically compared HUVEC proliferation, migration, invasion, and lumenogenesis in both mono- and co-culture conditions with PANC-1 (H-P). Subsequently, FcS treatment of the H-P system was evaluated for its anti-angiogenic properties. Molecular docking was utilized to predict the interactions between Formononetin and Salvianolic acid B with RhoA, and the post-treatment expression of RhoA in HUVECs was assessed. Furthermore, we utilized shRhoA lentivirus to elucidate the role of RhoA in FcS-mediated effects on HUVECs. In vivo, a zebrafish xenograft tumor model was employed to assess FcS's anti-tumor potential, focusing on cancer cell proliferation, migration, apoptosis, and vascular development. RESULTS: FcS treatment demonstrated a significant, dose-dependent inhibition of PANC-1-induced alterations in HUVECs, including proliferation, migration, invasion, and tube formation capabilities. Molecular docking analyses indicated potential interactions between FcS and RhoA. Further, FcS treatment was found to downregulate RhoA expression and modulated the PI3K/AKT signaling pathway in PANC-1-induced HUVECs. Notably, the phenotypic inhibitory effects of FcS on HUVECs were attenuated by RhoA knockdown. In vivo zebrafish studies validated FcS's anti-tumor activity, inhibiting cancer cell proliferation, metastasis, and vascular sprouting, while promoting tumor cell apoptosis. CONCLUSIONS: This study underscores the promising potential of FcS in countering pancreatic cancer-induced endothelial alterations. FcS exhibits pronounced anti-abnormal vasculature effects, potentially achieved through downregulation of RhoA and inhibition of the PI3K/Akt signaling pathway, thereby presenting a novel therapeutic avenue for pancreatic cancer management.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Traditional uses, botany, phytochemistry, pharmacology and applications of Labisia pumila: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, anti-inflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

Percepções e ações da equipe multiprofissional em saúde sobre a medicina tradicional indígena / Perceptions and actions of the multi-professional health team on traditional indigenous medicine / Percepciones y acciones del equipo multidisciplinario de salud sobre la medicina tradicional indígena

Objetivo: compreender as percepções e as ações de uma equipe multiprofissional em saúde quanto à prática da medicina tradicional indígena em uma Casa de Atenção à Saúde Indígena. Método: estudo qualitativo descritivo, realizado em uma de Casa de Apoio à Saúde Indígena em um município do Pará, que incluiu oito profissionais de uma equipe multiprofissional. A coleta de dados foi realizada no ano de 2018 e estes foram examinados pelo método da análise de conteúdo. Resultados: inserção e prática do cristianismo; ritos e lideranças xamânicas; e postura da equipe de multidisciplinar foram as categorias elencadas, que apontam os entendimentos e atuações da equipe multiprofissional e da organização espacial da Casa de Saúde do município. Considerações finais: há novos costumes e valores entre as etnias, em virtude da aproximação de grupos religiosos, cujas ações foram registradas e apreendidas pela equipe de trabalhadores em saúde.

Objective: understanding the perceptions and actions of a multi-professional health team regarding the practice of traditional indigenous medicine in an Indigenous Health Care Center. Method: this is a descriptive qualitative study carried out in an Indigenous Health Support Center in a municipality in the state of Pará, which included eight professionals from a multi-professional team. Data was collected in 2018 and examined using the content analysis method. Results: insertion and practice of Christianity; shamanic rites and leadership; and the attitude of the multidisciplinary team were the categories listed, which point to the understandings and actions of the multi-professional team and the spatial organization of the Health Center in the municipality. Final considerations: there are new customs and values among ethnic groups, due to the approach of religious groups, whose actions were recorded and apprehended by the team of health workers.

Objetivo: comprender las percepciones y acciones de un equipo multidisciplinario de salud sobre la práctica de la medicina tradicional indígena en una Casa de Atención para la Salud Indígena. Método: estudio descriptivo cualitativo, realizado en una Casa de Apoyo a la Salud Indígena de un municipio de Pará, que incluyó ocho profesionales de un equipo multidisciplinario. La recolección de datos se realizó en 2018 y los datos fueron sometidos al método de análisis de contenido. Resultados: inserción y práctica del cristianismo; ritos y líderes chamánicos; y actitud del equipo multidisciplinario fueron las categorías enumeradas, que indican la percepción y las acciones del equipo multidisciplinario y la organización espacial de la Casa de Salud del municipio. Consideraciones finales: existen nuevas costumbres y valores entre las etnias, debido a la presencia de grupos religiosos, el equipo de los trabajadores de la salud registró y aprendió las acciones de los indígenas.

Anemarrhena asphodeloides Bunge total saponins lower lipid via modulating MAOA activity to enhance defense mechanisms in mice and C. elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Within Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. AIM TO STUDY: This work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. MATERIALS AND METHODS: The characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. RESULTS: ABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. CONCLUSIONS: Our investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.

Exploring ethnic disparities in pediatric molluscum contagiosum in Southern Israel.

Molluscum contagiosum (MC) is a common skin infection affecting children globally, including in Israel, which has a diverse population comprising mainly Jews (73.2%) and Arabs (21.1%). Despite documented disparities in various diseases between these groups, research on differences in dermatological care is scarce. This study aimed to investigate MC as a potential differentiator between Arab and Jewish children. A retrospective analysis of MC cases among children (0-18 years) from 2013 to 2022 was performed at Soroka University Medical Center, a tertiary hospital serving over a million patients. 615 patients participated in our study, with 95.2% Jewish and 4.8% Arab. Both groups showed similar characteristics in lesion quantity (P = 0.535), diameter (P = 0.341), inflammation markers, and lesion location. Additionally, management, treatment response, and outcomes were found to be similar between the two groups. In conclusion, the Arab representation in the study was disproportionately low compared to their population in the area. While Jewish patients may rely more on medical specialists, we believe Arabs may prefer self-management practices, such as the use of traditional medicine, possibly hindering effective physician-led care. Understanding such disparities could improve dermatological care by tailoring approaches to diverse populations.

Effectiveness of the Traditional Japanese Medicine Goshajinkigan in Preventing Paclitaxel-Induced Peripheral Neuropathy: A Multicenter Randomized Comparative Trial.

Objective: Development of chemotherapy-induced peripheral neuropathy (CIPN) poses significant challenges in cancer treatment, often leading to dose reductions or treatment discontinuation. Goshajinkigan (GJG), a traditional Japanese medicine, has shown promise for alleviating CIPN symptoms. This multicenter, randomized controlled trial aimed to prospectively examine the efficacy of GJG in preventing paclitaxel-induced peripheral neuropathy. Methods: This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. The participants were randomized into Groups A (GJG initiation after onset of grade 2 neuropathy) and B (prophylactic administration of GJG from 1 week before chemotherapy). The primary endpoints were the proportion with a maximum sensory neuropathy grade and visual analog scale (VAS) scores. The secondary endpoints were the rate of chemotherapy completion and paclitaxel dose reduction due to neurotoxicity. Results: Prophylactic GJG administration (Group B) resulted in significant benefits. While both groups had a similar incidence of grade 2 sensory neuropathy, all patients in Group B with grade 2 neuropathy completed treatment without requiring additional analgesics. Group B exhibited lower VAS scores by the end of the study, reduced reliance on adjuvant analgesics (27.3% vs 66.7% in Group A), and significantly less frequent persistent CIPN 6 months post-chemotherapy (18.2% vs 55.6% in Group A). No differences were observed in the chemotherapy completion rates or CIPN-related changes between the groups. Conclusion: GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings.

Prevalence and distribution of intestinal parasitic infections in taeniasis endemic area of North Sumatera, Indonesia.

A group of helminthic and intestinal protozoa causes intestinal parasitic infections (IPIs), affecting more than 2.5 billion people worldwide. IPIs are diseases closely associated with poor hygiene and sanitation, concentrated in underdeveloped regions and among populations with low socioeconomic status. Consequently, most prevalence is in Sub-Saharan Africa and Asia, with local habits or risk factors that could affect its prevalence. The aim of this study was to determine how hygienic practices, sanitation, and local behavior of eating raw meat (hinasumba) contributed to the prevalence of IPI. A cross-sectional study was conducted in the Simalungun District of North Sumatera Province, involving 428 people of Batak Simalungun. There were 15 villages randomly selected across the district based on the local registry, which consequently, non-purposive sampling was conducted. Face-to-face interviews assessed various risk factors, such as demographic characteristics, water source, traditional raw meat consumption, or hinasumba as local risk factors, hygienic practices, and sanitation. The findings indicated that an overall prevalence rate of IPI was 42.9%, consisting of 87.5% with helminthic infection and 12.5% with protozoal infection. More than half of IPI cases were associated with Taenia sp. infections (21.8%), followed by hookworms' infections with a 6.1% positivity rate. Based on multivariate analysis, farming and consuming traditional delicacies, namely hinasumba, increased the likelihood of IPI occurrence among the population by 1.7 and 3 times, respectively. It can be concluded that the high prevalence of taeniasis in the study area was associated with local behavior and hinasumba consumption, which may contribute to determining the dominance of specific IPI species.

Bioaccessibility and bioavailability of exogenous and endogenous toxic substances in traditional Chinese medicine and their significance in risk assessment.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

Surface and deep learning: a blended learning approach in preclinical years of medical school.

BACKGROUND: Significant challenges are arising around how to best enable peer communities, broaden educational reach, and innovate in pedagogy. While digital education can address these challenges, digital elements alone do not guarantee effective learning. This study reports a blended learning approach integrating online and face-to-face components, guided by the Student Approaches to Learning framework. METHODS: This study was carried out investigating learning in first and second year medical students over two academic years, 2019/20 and 2020/21. We evaluated: (1) comparison of students engaged with blended learning and traditional learning; and (2) student learning engaged with blended learning approach over a two-year preclinical curriculum. A revised two-factor study process questionnaire (R-SPQ-2F) evaluated students' surface/deep learning before and after an academic year. Learning experience (LE) questionnaire was administered over the domains of learning engagement, and outcomes of learning approach. In-depth interviews were carried out to understand the context of students' responses to the R-SPQ-2F and LE questionnaires. RESULTS: The R-SPQ-2F analysis indicated first year students maintained deep learning but second year students became neutral across the academic year, regardless of learning approach, with workload contributing to this outcome. R-SPQ-2F sub-scales showed that students engaged with blended learning maintained an intrinsic interest to learning, as compared to traditional learning which led to surface learning motives. The LE questionnaire showed students engaged with blended learning had deeper subject interest, and more positive perceptions of workload, feedback, and effectively developed skills and knowledge. However, peer interactions from blended learning were significantly lacking. In-depth interviews revealed that the flexibility and multi-modality of blended learning enabled learning, but the best use of these features require teacher support. Online interactions could be cultivated through intentional institutional efforts. CONCLUSIONS: This study highlights the importance of designing blended learning that leverages technology-enabled flexibility while prioritising collaborative, learner-centred spaces for deep engagement and knowledge construction.

Can family structure and contact with natural resources influence young people's knowledge about medicinal plants? An approach in the Northeast of Brazil.

BACKGROUND: Individuals develop crucial survival knowledge in the juvenile phase, including understanding medicinal plants. The family context or contact with resources can influence this dynamic knowledge. By investigating the influence of these factors on young people's understanding of medicinal plants, we aimed to enhance our understanding of the knowledge-building process. METHODS: The study was conducted in three communities in the State of Alagoas, Brazil: Lagoa do Junco, Serrote do Amparo, and Brivaldo de Medeiros. Semi-structured interviews were conducted with young people aged between 11 and 19 to assess their knowledge of medicinal plants. We used a generalized linear mixed model (GLMM) with the number of therapeutic targets and known medicinal species (knowledge proxy) as response variables. As predictors, we included the number of individuals per family unit and the gender distribution within the famimunícpily (family context proxy), as well as dependence on the use (contact proxy). Location (city) was added as a fixed effect to the model. We investigated how knowledge of medicinal plants correlates with the practice of collecting these species. RESULTS: We did not identify a relationship between the number of individuals per household, gender distribution within the family, and the frequency of medicinal plant use with knowledge about these species. However, we observed a positive, albeit weak, correlation between knowledge of medicinal species and the number of species collected. CONCLUSION: These results highlight the importance of investigating how young people acquire knowledge about medicinal plants, emphasizing the complex interactions between humans and nature, and providing a basis for future research.

Ethnobotanical survey and scientific validation of liver-healing plants in northeastern Morocco.

Introduction: Liver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis. Methods: An ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented. Results: The survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health. Discussion: The study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants. Conclusion: This ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims.

ER stress modulates Kv1.5 channels via PERK branch in HL-1 atrial myocytes: Relevance to atrial arrhythmogenesis and the effect of tetramethylpyrazine.

Endoplasmic reticulum (ER) stress is implicated in cardiac arrhythmia whereas the associated mechanisms remain inadequately understood. Kv1.5 channels are essential for atrial repolarization. Whether ER stress affects Kv1.5 channels is unknown. This study aimed to elucidate the response of Kv1.5 channels to ER stress by clarifying the unfolded protein response (UPR) branch responsible for the channel modulation. In addition, the effect of tetramethylpyrazine (TMP) on Kv1.5 channels was studied. Patch clamp and western-blot results revealed that exposure of HL-1 atrial myocytes to ER stress inducer tunicamycin upregulates Kv1.5 expression, increases Kv1.5 channel current (I Kur ) (14.91 ± 1.11 vs. 6.11 ± 1.31 pA/pF, P < 0.001), and shortened action potential duration (APD) (APD90: 82.79 ± 5.25 vs.121.11 ± 6.72 ms, P < 0.01), which could be reverted by ER stress inhibitors. Blockade of the PERK branch while not IRE1 and ATF6 branches of UPR downregulated Kv1.5 expression, accompanied by a decreased I Kur (9.03 ± 0.99 pA/pF) and a prolonged APD90 (113.69 ± 4.41 ms) (P < 0.01). PERK-mediated increases of Kv1.5 expression and I Kur were also observed in HL-1 cells incubated with thapsigargin. TMP suppressed the enhancement of I Kur (10.52 ± 0.97 vs. 17.52 ± 2.25 pA/pF, P < 0.05), prevented the shortening of APD (APD90: 110.16 ± 5.36 vs. 84.84 ± 4.58 ms, P < 0.05), and inhibited the upregulation of Kv1.5 triggered by ER stress. Our study suggests that ER stress induces upregulation and activation of Kv1.5 channels in atrial myocytes through the PERK branch of UPR. TMP prevents Kv1.5 upregulation/activation and the resultant APD shortening by inhibiting ER stress. These results may shed light on the mechanisms of atrial arrhythmogenesis and the antiarrhythmic effect of the traditional Chinese herb TMP.

The Impact of Minimum Invasive Access Cavity Design on the Quality of Instrumentation of Root Canals of Maxillary Molars Using Cone-Beam Computed Tomography: An in Vitro Study.

Aim Minimally invasive dentistry has been facilitated by advances in instruments and restorative materials. This study aims to compare the change in the shaping ability of the RECIPROC blue rotary system in both traditional and conservative access cavities, using cone beam computed tomography (CBCT). Material and methods Sixty root canals of 20 artificial maxillary molars were assigned into two groups (n=30 root canals) according to the access cavity design used: Group I: traditional access cavity (TAC) and Group II: conservative access cavity (CAC). CBCT scans of samples were made before and after root canal preparation using the RECIPROC blue rotary system. The shaping parameters are evaluated in root canal transportation and the centering ability. Three CBCT sections per tooth were analyzed at 3, 6, and 9 mm from the apex to assess the canal transportation and centering ability at three levels, apical, middle, and coronal thirds. Data were analyzed using the GraphPad Prism (GraphPad Software, San Diego, CA). Results The results of this study showed a significant difference in transportation within the coronal and middle thirds. However, in apical thirds, there were no significant differences. Both groups observed a significant difference in the centering ability in the coronal third. Conclusion Within the limitations of this study, CAC can be recommended with caution as an alternative access to TAC.

Disparities in hepatitis C among people aged 12-59 with no history of injection drug use, United States, January 2013-March 2020.

BACKGROUND AND AIMS: In the United States, hepatitis C virus (HCV) infection occurs primarily through injection drug use (IDU), but transmission also occurs through other ways. This study examined HCV prevalence and disparities among US residents aged 12-59 years with no IDU history. METHODS: We analysed 2013-March 2020 National Health and Nutrition Examination Survey data to calculate the HCV prevalence among people with no drug use history and only a non-IDU history, collectively referred to as no IDU history. These estimates were compared to those with an IDU history and stratified by sociodemographic and hepatitis A and hepatitis B serologic characteristics. RESULTS: The current HCV infection prevalence among people aged 12-59 was .7% overall, and specifically 17.2% among people with an IDU history, .9% among people with a non-IDU history and .2% among people with no drug use history. These rates represented 1.4 million people with current HCV infection, of whom, 730 000 had an IDU history, 262 000 had a non-IDU history and 309 000 had no drug use history. Among people with no drug use history, current HCV infection prevalence was higher for people born during 1954-1965 versus after 1965, had completed high school or less versus at least some college and had past/present hepatitis B versus vaccinated for hepatitis B. CONCLUSION: While the HCV infection burden was highest among people with an IDU history, we found a sizeable burden among people without such a history. These findings support policies and practices aimed at addressing disparities among people needing treatment.

Conventional Therapy Combined With Quxie Capsule Modulating Gut Microbiome in Metastatic Colorectal Cancer Patients With the Third or Above Line Setting: Result From an Investigator-Initiated, Open-Label, Single-Arm, Phase II Study.

BACKGROUND: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)-a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)-has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. METHODS: A Simon's Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. RESULTS: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae, Eubacterium and Lachnospiraceae_UCG-001. CONCLUSIONS: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100053874).

Metabolomics integrated with network pharmacology of blood-entry constituents reveals the bioactive component of Xuefu Zhuyu decoction and its angiogenic effects in treating traumatic brain injury.

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. OBJECTIVES: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. METHODS: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. RESULTS: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. CONCLUSION: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Analysis of the region-specific characteristics of traditional Korean doenjang produced in Gyeonggi-do.

Doenjang is traditional soybean fermented food in Korea, and traditional doenjang on the market has different qualities like aroma, taste. This study is a preliminary study to investigate the quality characteristics of doenjang produced in each region of Korea. The objective of this study was to analyze the region-specific characteristics of traditional Korean doenjang produced in Gyeonggi-do. Physiochemical characteristics including pH, moisture content, soluble solid content, salinity, color, acid value, titratable acidity, NH2-N, total/reducing sugar, and alcohol contents, and enzymatic activities such as acidic/neutral protease and α/ß-amylase activities, were analyzed. Doenjang produced in Gyeonggi-do was classified into two groups (GDG-A and GDG-B), and the distinction between two groups were the aging period: doenjang samples in GDG-A groups were aged over 3 yrs, while samples in GDG-B groups were aged less than 3 yrs. The results of this study provided the physicochemical characteristics and enzymatic activities of traditional doenjang produced in Gyeonggi-do.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment.

BACKGROUND: Prostate cancer (PCa) has high morbidity and mortality rates in elderly men. With a history of thousands of years, traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis, enhance therapeutic effects, and reduce the risk of recurrence and metastasis. Multiple studies have shown that Coridius chinensis (Cc) has anticancer effects. AIM: To elucidate the mechanism of action of Cc against PCa via network pharmacology and molecular docking. METHODS: Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software, the PharmMapper database and the GeneCards database. Then, the STRING database was used to construct the protein-protein interaction network. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and molecular docking analyses were subsequently conducted to identify the key targets, active ingredients and pathways involved. RESULTS: GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway (P value < 1.0 × 10-8). Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc. Seven active compounds (asponguanosines A, asponguanine B, asponguanine C, aspongpyrazine A, N-acetyldopamine, aspongadenine B and aspongpyrazine B) were selected for molecular docking with 9 potential targets, and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa (affinity<-5 kcal/mol, hydrogen bonding), but more studies are needed. CONCLUSION: We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa, supporting the development of Cc as a natural anticancer agent.

The effect of different traditional Chinese exercises on bone mineral density in menopausal women: a systematic review and network meta-analysis.

Objective: To evaluate the optimal choice of traditional Chinese exercise (TCE) for improving bone mineral density in postmenopausal women through a network meta-analysis. Methods: The Chinese and English databases were searched, including China National Knowledge Infrastructure, Chongqing VIP, PubMed, Web of Science and Cochrane Library. The outcomes included BMD of lumbar L2-L4, femoral neck, ward triangle, and greater trochanter. Standardized mean differences (SMD) and 95% confidence intervals (CI) were used to assess the correlation between each group of interventions, and surface under the cumulative ranking (SUCRA) was used to rank the best interventions. Results: A total of 20 randomized controlled trials (RCTs) including 1933 subjects and six interventions: [Tai Chi (TC), Baduanjin (BDJ), Wuqinxi (WQX), Yijinjing (YJJ), TA (Tai chi plus calcium supplementation), BA (Baduanjin plus calcium supplementation)] and three control measures: [Calcium supplementation (CA), Aerobic exercise (AE), Not exercise intervention (NEI)] were analyzed. Regarding BMD of lumbar L2-L4: TC [SMD = 0.99 (0.62, 1.37)], BDJ [SMD = 2.12 (1.39, 2.85)], TA [SMD = 1.12(0.17, 2.07)], BA [SMD = 2.24 (1.16, 3.31)] were superior in increasing BMD of lumbar L2-L4 relative to NEI. Regarding BMD of femoral neck: TC [SMD = 1.24 (0.70, 1.78)], BA [SMD = 3.77 (1.98, 5.56)] were superior in increasing BMD of femoral neck relative to NEI. Regarding BMD of ward's triangle: TC [SMD = 1.63 (1.09, 2.17)] was superior in increasing BMD of ward's triangle relative to NEI. Regarding BMD of greater trochanter: TC [SMD = 0.98 (0.28, 1.68)] were superior in increasing BMD of greater trochanter relative to NEI. TC topped the SUCRA with BMD of lumbar L2-L4: 53.8, femoral neck: 74.9, ward's triangle: 86.9 and greater trochanter: 77.7. Conclusion: Four TCE (TC, BDJ, TA and BA) are all effective in partially improving BMD indicators in postmenopausal women, while TC was effective on all four BMD indicators, which seems to be recommended as the most suitable exercise modality for postmenopausal women. Systematic review registration: This research follows the PRISMA Network statement. The protocol for this study has been registered in the International Prospective Registry of Systematic Reviews (PROSPERO). CRD42023414944.