Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights.

Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti-inflammatory, antioxidant, anti-apoptotic, and anti-tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.

Small Extracellular Vesicles Promote Stiffness-mediated Metastasis.

Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiologic matrix stiffness affects the quantity and protein cargo of small extracellular vesicles (EV) produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2ß1, ITGα6ß4, ITGα6ß1, CD44) compared with EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix proteins including collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer-associated fibroblast phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment. SIGNIFICANCE: Here we show that the quantity, cargo, and function of breast cancer-derived EVs vary with mechanical properties of the extracellular microenvironment.

Screening parent-adolescent relationships, screen behaviors, tridimensional acculturation, and health among Black immigrant and refugee adolescents during dual pandemics.

This brief report assesses parent-adolescent relationships, screen behaviors, and tridimensional acculturation as risk and promotive or protective factors for health among Black U.S. immigrant or refugee adolescents during the dual COVID-19 and racism or Whiteness pandemics. Eighty-nine immigrant- or refugee-origin adolescents completed online surveys (72% Somali American, 28% Jamaican American; 45% female; 15% foreign-born; M = 14.11 years). Regression analyses revealed that parental autonomy support, parental restrictive media mediation, and adolescent heritage culture identification were promotive of better screen media use behaviors. Only adolescent media literacy self-efficacy was related to higher screen time. Importantly, screen self-regulation was a better predictor of general health than screen time. Results highlight many parenting strengths in Black immigrant or refugee families and underscore the resilience-promoting power of parent-adolescent relationships. Health implications are discussed to provide guidance for future prevention efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ethical applications of digital community-based research with Black immigrant and refugee youth and families.

The capacity to conduct psychology research online has expanded more quickly than have ethics guidelines for digital research. We argue that researchers must proactively plan ways to engage ethically in online psychological research with vulnerable groups, including marginalized and immigrant youth and families. To that end, this article describes the ethical use of internet and cell phone technologies in psychological research with Black immigrant and refugee youth and families, which demands efforts to both deepen and extend the Belmont principles of respect for persons, beneficence, and justice. We describe and apply four research frameworks-community-based participatory research, transdisciplinary team science, representational ethics, and cross-cultural psychology-that can be integrated to offer practical solutions to ethical challenges in digital research with Black immigrant and refugee youth and families. Then, as an illustration, we provide a case example of this approach using the Food, Culture, and Health Study conducted with Black Jamaican American and Somali American youth and families, who experience tridimensional acculturation due to their race and have been disproportionately impacted by the dual pandemics of COVID-19 and racism/Whiteness. We offer this article as a road map for other researchers seeking to conduct ethical digital community-based psychological research with Black immigrant youth and families and other marginalized communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Small extracellular vesicles promote stiffness-mediated metastasis.

Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiological matrix stiffness affects the quantity and protein cargo of small EVs produced by cancer cells, which in turn drive their metastasis. Primary patient breast tissue produces significantly more EVs from stiff tumor tissue than soft tumor adjacent tissue. EVs released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα 2 ß 1 , ITGα 6 ß 4 , ITGα 6 ß 1 , CD44) compared to EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix (ECM) protein collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination through enhanced chemotaxis. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer associated fibroblast (CAF) phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment.

Efficacy of resveratrol in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.

Polycystic ovarian syndrome (PCOS) is a metabolic and hormonal condition affecting women of a reproductive age. It causes an abnormal menstrual cycle, anovulation, infertility, acne, hirsutism, obesity, hyperlipidemia, and cardiovascular disorders. Because resveratrol decreases testosterone levels, it may be of value in treating PCOS. We aimed to evaluate the efficacy of resveratrol in treating women with PCOS. We searched for randomized clinical trials (RCTs) in PubMed, Cochrane CENTRAL, Scopus and Web of Science. With 95% confidence intervals, the data was retrieved and analyzed as a mean difference (MD) or a standardized mean difference (SMD). Four RCTs with 218 women were included in the analysis. Resveratrol significantly reduced testosterone (SMD = -0.40; 95% CI [-0.71, -0.10], P = 0.009), luteinizing hormone (LH) (SMD = -0.32; 95% CI [-0.62, 0.01], P = 0.04), and dehydroepiandrosterone sulfate (DHEAS) (MD = -0.85; 95% CI [-1.25, -0.45], P < 0.0001) compared with the placebo. Resveratrol is effective in treating women with PCOS due to reducing the levels of testosterone, LH, and DHEAS. In combination with other treatments, especially for hyperlipidemia, resveratrol is beneficial for women diagnosed with PCOS.

WhatsApp supervision for a lay-led Islamic trauma-focused intervention in Somaliland: Qualitative content analysis.

Clinical supervision is critical for the uptake of psychotherapy but difficult to facilitate in countries with limited providers, resources, and internet infrastructure. Innovative supervision approaches are needed to increase access to mental health treatments in low-to-middle income countries (LMICs). This study examined the content and feasibility of remote WhatsApp text supervision conducted as part of an open clinical trial in Somaliland. Islamic Trauma Healing ITH) is a brief, group, lay-lead, trauma-focused, mosque-based intervention that has demonstrated initial efficacy in pilot studies in the United States and Somaliland. After a 2-day, in-person training, lay leaders led four groups of five to seven members focused on trauma-related psychopathology and community reconciliation. Somali lay leaders trained in ITH (n = 9) and the research team (n = 6) attended weekly WhatsApp supervision during the intervention. Content was logged and subjected to qualitative analysis by two coders. Comments related to intervention implementation indicated that lay leaders understood the treatment rationale, adhered to treatment procedures, and believed the intervention components to be helpful and culturally relevant. Themes related to engagement suggested perfect attendance across groups and high levels of participation. Lay leader psychoeducation and skill development; supervisor praise, support, and encouragement; and supervisee gratitude emerged as additional themes. Remote text supervision conducted via WhatsApp was technologically feasible and may have facilitated skill development and the effective implementation of this lay-led intervention. When tailored to the local context, remote supervision approaches hold promise for increasing access to services in LMICs with limited resources.

A Novel Blueprint Storyboarding Method Using Digitization for Efficient Cultural Adaptation of Prevention Programs to Serve Diverse Youth and Communities.

There is a pressing need for prevention programs that address increasing rates of epidemics and pandemics, including noncommunicable diseases. However, many populations face substantial systemic barriers to accessing traditional prevention programs. To minimize persistent service utilization gaps for underserved populations, the field requires effective, efficient, and sustainable methods to increase accessibility and cultural relevance of prevention programming to multiple audiences. Cultural adaptation is one such strategy, but it can be daunting for many preventionists. Therefore, this paper presents a step-by-step guide to streamline the cultural adaptation of prevention programs through digitization and use of a novel application of storyboarding methodology, called "blueprint storyboarding." This innovative approach to cultural adaptation is designed to increase systematicity through manualization, efficiency, cost-effectiveness, and adaptability for multiple cultures and developmental stages. We illustrate this novel method by describing how we applied the blueprint storyboarding approach after digitization to culturally adapt the JUS Media? Programme, a food-focused media literacy program designed to buffer media-related obesity risks for diverse youth.

Analysis of Marrubiin in Marrubium alysson L. Extract Using Advanced HPTLC: Chemical Profiling, Acetylcholinesterase Inhibitory Activity, and Molecular Docking.

The main purpose of this work is to investigate the phytochemical composition of Marrubium alysson L. non-polar fraction. GC/MS analysis was used to evaluate the plant extract's saponifiable and unsaponifiable matter. Although M. alysson L. lipoidal matter saponification produced 30.3% of fatty acid methyl esters and 69.7% of unsaponifiable matter. Phytol was the most dominant substance in the unsaponifiable materials. Notably, marrubiin which is one of the most prominent metabolites of Marrubium alysson L. was not detected through our adopted GC/MS technique. Thus, further characterization was proceeded through simple and rapid HPTLC analysis which successfully managed to identify marrubiin. Based on the regression equation, the concentration of marrubiin in M. alysson L. extract was 14.09 mg/g of dry extract. Concerning acetylcholinesterase inhibitory activity, both the crude M. alysson L. total methanolic extract and the non-polar fraction displayed reasonable inhibitory activity against acetylcholinesterase (AChE), whereas the pure compound marrubiin was considered to be the most effective and potent AChE inhibitor, with an IC50 value of 52.66 (µM). According to the molecular docking studies, potential sites of interaction between the pure chemical marrubiin and AChE were examined. The results show that Tyr124 on AChE residue was critical to the activity of the aforementioned drug. Based on the depicted marrubin AChE inhibition activity and reported safety profile, this chemical metabolite is considered as a promising lead compound for further pre-clinical investigation as well as drug development and optimization.

Marrubium alysson L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling.

Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether Marrubium alysson L. (M. alysson L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of M. alysson L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of M. alysson L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level versus MTX alone. Significant down-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of M. alysson L. displayed a more pronounced decline in the testicular levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, M. alysson L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of M. alysson L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode.

Assessing the suitability of a two-dimensional array for routine quality assurance checks of flatness and symmetry.

Quality assurance of radiotherapy linear accelerator beams demands the use of equipment with high resolution and reliability of reproducible results over time. This study examines the suitability of a commercially available two-dimensional ionization chamber array-the StarCheck array (PTW, Frieburg, Germany) to measure symmetry and flatness for both photon and electron beams. The study was conducted over a period of 4 years whereby the reliability of the array could be established. The reproducibility, uniformity of chamber response, and comparison of both photon and electron profiles acquired with the StarCheck array to that of the water-tank were examined. The most significant result was that across all profiles acquired using the StarCheck array, a defective chamber was detected, manifested by a 'dip' in the cross-plane profile at the same position. Assuming all detectors are functional, StarCheck was shown to be within 1% of the water-tank results for both flatness and symmetry. The detector array exhibited many calibration and detector issues over the period in which it has been used in the department. Furthermore, PTW recommends that recalibration of the array should to be performed every 2 years at either PTW, Freiburg, or at a qualified calibration laboratory. Therefore, the department requires a backup device for the recalibration time, approximately 4 months as worst case.

Correction to: Role of identified bacterial consortium in treatment of Quhafa wastewater treatment plant influent in Fayuom, Egypt.

The original version of this article unfortunately contained an error.

Role of identified bacterial consortium in treatment of Quhafa Wastewater Treatment Plant influent in Fayuom, Egypt.

This study was aimed to biologically treat domestic wastewater using identified bacterial consortium for chemical pollutants removal by treating/passing it through sand biofilters. The identification, toxicity test, and the optimum dose of the investigated bacterial consortium were carried out using Microtox analyzer and Batch biological treatment, respectively. Furthermore, application of sedimentation followed by gravel and sand biofilters for wastewater treatment was evaluated. The results showed that the bacterial consortium is composed of Pediococcus acidilactici, Pediococcus pentosaceus, Lactobacillus plantarum, and Bacillus subtilis. The optimum dose for wastewater treatment within 6 h of contact time is 2.5 mg/L, this dose (2.5 mg/L) has no toxic effect. The removal percentage of chemical oxygen demand (COD), biological oxygen demand (BOD), total solids (TS), total dissolved solids (TDS), total suspended solids (TSS), ammonia, nitrate, total Kjeldahl nitrogen (TKN), and oil and grease reached 93.4, 83.5, 37.5, 49.2, 93.4, 100, 55.7, 76.6, and 76% in the effluent of the treated wastewater, respectively after the third sand biofilter filtration. It can be concluded that using bacterial consortium for domestic wastewater treatment could be a good tool for chemical pollutants removal. Moreover, this study provides low cost and eco-friendly tool for domestic wastewater treatment using simple multistage biofilters based on an identified bacterial consortium. This system can be upscaled for the treatment of larger volumes of wastewater.

Design of a bioaugmented multistage biofilter for accelerated municipal wastewater treatment and deactivation of pathogenic microorganisms.

Biological treatment of municipal wastewater for reuse in irrigation is highly required, especially with the current global financial and water shortage crises. Bioaugmentation is a simple and cost-effective technology which could be a useful tool in alleviating this challenge. Thus, this study aimed to enhance the biological treatment of municipal wastewater using a bioaugmented substance supplemented in a three-stages bio-filter consisting of a sedimentation step followed by gravel biofiltration and then sand biofiltration at a laboratory scale. Also, a toxicity assay, the antimicrobial effect of the bioaugmented substance against pathogenic microorganisms, and identification of the synergistic effect of the bacterial consortium involved in the bioaugmented substance were studied. The bioaugmented substance was nontoxic and had an antimicrobial effect against the tested potentially pathogenic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus, and Candida albicans). The minimum effective concentration of the bioaugmented substance for organic, inorganic and microbial pollutants removal from high strength wastewater was 2.5 ppm with a contact time of 6-8 h. The removal efficiencies of H2S, COD, BOD5, total solids (TS), total dissolved solids, total suspended solids, ammonia, nitrate, phosphorus, and oil and grease reached 85, 93.4, 83.5, 37, 49.2, 93.4, 100, 55.7, 76.6 and 76.6%, respectively in the treated effluent after sand biofiltration. The physicochemical parameters of the treated wastewater effluent were below the Egyptian recommended limits (Law 84/1984) for use in irrigation. However, COD and BOD values were 90.33 and 38.46 mgO2/L, respectively, and were still above the regulations (COD ≤60 and BOD ≤20). The high fecal coliforms count in the wastewater influent (8.4 × 108 MPN-index/100 mL) were 95.1% removed after the sedimentation stage, and 99.99% removal was achieved after gravel and sand biofiltration. Thus, this study successfully designed a bioaugmented multistage biofiltration system for the effective removal of pollutants from wastewater, especially in resource-limited areas.

Competing Endogenous RNAs in Hepatocellular Carcinoma-The Pinnacle of Rivalry.

The role of noncoding transcripts in gene expression is nowadays acknowledged to keep various diseases at bay-despite being referred to as "junk" DNA several years ago. Believed to be at the heart of multiple regulatory pathways, microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in posttranscriptional gene regulation. Recently, the discovery of ncRNAs that compete for shared miRNA pools has dimmed the light on the solo performance of miRNAs in genomic regulation. Indeed, several studies describe RNAs such as long noncoding RNAs, mRNAs, circular RNAs, pseudogenes, and viral RNAs as competing endogenous RNAs (ceRNAs) that sequester miRNAs, allowing for de-repression of downstream miRNA targets. Such integration between coding and noncoding transcripts forms complex ceRNA networks that when dysregulated lead to several diseases such as hepatocellular carcinoma. Here, the authors review perturbed ceRNA networks in hepatocellular carcinoma, describe the role of each in tumorigenesis, and discuss their various clinical implications.

Audit of acute asthma management at the Paediatric Emergency Department at Wad Madani Children's Hospital, Sudan.

This audit of hospital care of acute wheeze and asthma aimed to assess the degree of adherence of the acute care of the asthma patients to the published international guidelines. Information was collected in six key areas: patient demographics; initial asthma severity assessment; in-hospital treatment; asthma prophylaxis; asthma education and emergency planning; and follow-up arrangements. The area of initial asthma severity assessment showed defciencies in the clinical measures currently used to verify case severity. In- hospital treatment on the other hand was consistent with recommendations in the use of the inhaled ß-2 agonist salbutamol as bronchodilator, the discrete use of aminophylline and the small number of patients ordered chest X-ray. However, the treatment was incoherent with recommendations in the delivery method used for inhaled bronchodilator in relation to the age group of treated patients, absence of ipratropium bromide as a bronchodilator in the management and the large use of antibiotics. Assessment of the areas of asthma prophylaxis, asthma education and emergency- planning and follow-up arrangements illustrated that little efforts were made to assure safe discharge, although these measures have been shown to reduce morbidity after the exacerbation and reduce relapse rates and signifcantly reduce hospitalizations, unscheduled acute visits, missed work days, as well as improving quality of life. This audit emphasizes the need for the adoption of a management protocol for acute asthma care in the emergency department based on published international guidelines and the assurance of its implementation, monitoring and evaluation using the right tools to improve patient care.

Long-term mortality in patients with pauses in ventricular electrical activity.

BACKGROUND: The long-term significance of ventricular pauses of > or =3.0 seconds observed on Holter monitor is unclear, as previously conducted retrospective studies have been poorly controlled. We compared the prognosis of patients with pauses > or =3.0 seconds on Holter monitor with a well-matched control group without such pauses. METHODS: Scanning the Holter database at Ochsner Clinic (n = 11,730; January 1998 to June 2003) for pauses > or =3.0 seconds identified 70 patients (pause group). Of those, 29 (37.1%) received a permanent pacemaker (PPM group) and 41 (62.9%) did not (No-PPM group). For each No-PPM patient, two patients without pauses (<2.0 seconds) exactly matched for age, sex, ejection fraction (EF), rhythm, and duration of follow-up were randomly chosen from the Holter database (control group, n = 82) and survival of the two groups was compared. RESULTS: Mean age was 72.5 +/- 15.0 years, mean EF was 52.2 +/- 12.7%, and 68.3% were men. Mean follow-up was 2.2 years (0.5-4.5 years). There was no difference in survival between the No-PPM and the control groups (82.9% vs 84.1%, P = NS). Compared with the PPM group, pauses in the No-PPM group were more commonly asymptomatic, nocturnal, and due to sinus pauses or atrial fibrillation (AF) with slow ventricular response. CONCLUSIONS: Pauses in ventricular electrical activity > or =3 seconds on Holter monitor due to sinus pauses or AF with slow ventricular response are not predictive of heightened mortality.

Relation between left ventricular geometry and transmural dispersion of repolarization.

Studies have shown an association between left ventricular (LV) geometry and complex ventricular ectopic activity. Increased transmural dispersion of repolarization (TDR), which correlates to the interval from the peak to the end of the T wave (Tpe) on the surface electrocardiogram, is linked to ventricular tachyarrhythmias. The relation between LV geometry and TDR is unknown. The mean Tpe interval, measured from leads V(1) to V(3) of the surface electrocardiogram, was assessed in 300 patients (50% men) who had normal LV systolic function and QRS duration and were categorized into 3 equal groups, which were matched by age and gender, according to echocardiographically determined LV geometry (normal structure, concentric remodeling, and LV hypertrophy). The Tpe interval was corrected for the QT interval using Tpe/QTc and was compared among the 3 groups. Compared with those who had normal LV structure, the Tpe interval was significantly prolonged in those who had LV hypertrophy and significantly shortened in those who had concentric remodeling (p = <0.0001 for the 2 comparisons). Correcting for the QT interval using Tpe/QTc yielded similar results. Thus, TDR was increased in patients who had LV hypertrophy but decreased in concentric remodeling compared with those who had normal cardiac structure. Although LV hypertrophy represents a maladaptive geometric process that results in an unfavorable electrical substrate, concentric remodeling may represent a structural adaptation that has a more favorable electrical milieu.