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Context: Berberis aristata DC (Berberidaceae) is an important medicinal plant with claims of widespread medicinal value in indigenous medicine. It is used by herbal healers to treat oral cancers. Objective: To evaluate the antineoplastic activity of the extracts of Berberis aristata in Ehrlich ascites carcinoma (EAC)-bearing mice with cisplatin as positive control in the advanced stage of tumorigenesis. Materials and methods: Brine shrimp lethality bioassay (BSL) of extracts and effect on the tumor cell viability in vitro were carried out. EAC was induced in Swiss albino mice by injecting 106 cell/mL of tumor cell suspension i.p. Antineoplastic activity of the aqueous and ethanol extracts (100 and 6.5 mg/kg i.p., respectively) was compared with that of cisplatin (3.5 mg/kg i.p.) on the parameters such as percentage increase in weight, median survival time, and hematology. Results: Ethanol extract attenuated percentage increase in weight gain (−6.86 ± 1.50) due to tumor cell proliferation and increased the survival time (19.5 days) when compared to control group (19.10 ± 2.31 and 16 days, respectively). However, the effect was less than that of cisplatin. In vitro cytotoxicity assay as well as BSL test showed the cytotoxic effect of the extracts. Cisplatin and the extracts reversed the tumor-induced alterations in total white blood cell count, differential leukocyte counts, total red blood cell count, and hemoglobin contents. Discussion and conclusion: Of the two extracts, the ethanol extract was observed to be more efficient and the presence of alkaloids and flavonoids may be responsible for the observed anticancer effects. [ABSTRACT FROM AUTHOR]

Purpose - The paper attempts to provide a structured process for consumer packaged goods (CPG) companies which wish to implement sales portals in their organizations. Design/methodology/approach - The approach to the framework is largely derived from the authors' experience with CPG companies. It also involves reference to some secondary information. The paper also presents an example of a case study to validate the benefits of a structured approach to sales portal implementation. Findings - The paper throws light on why CPG companies fail to implement sales portals and prescribes a three-step approach to streamline the implementation process. Practical implications - The paper presents a ready guide on what needs to be considered while implementing a sales portal across different channel partners. Originality/value - The paper is an original work based on rich experience in the CPG field and provides a simple method for companies planning to implement sales portals. [ABSTRACT FROM AUTHOR]

Generation of free radicals in the kidney cortex plays an important role in the pathogenesis of cisplatin-induced dysfunction of renal proximal tubule cells. Previous studies carried out showed that an alcohol extract ofCrataeva nurvalastem bark possessed antioxidant activity in rats, hence the present work aimed at evaluating the possible effect of the alcohol extract ofC. nurvalaon cisplatin-induced dysfunction model of renal proximal tubule cells by oxidative stress. The alcohol extract was administered orally for ten days at two dose levels of 250 and 500  mg/kg body weight, five days after administration of a single i.p. dose of cisplatin(5  mg/kg). Renal dysfunction was evaluated histologically by light microscopy and biochemically by measuring the concentrations of blood urea nitrogen, serum creatinine, lipid peroxidation, glutathione and catalase activity in the kidney cortex. The results suggest that the plant extract(250 and 500  mg/kg)was effective in significantly altering the indices of cisplatin induced dysfunction of renal proximal tubule cells under oxidative stress by decreasing the concentration of blood urea nitrogen, creatinine and lipid peroxidation. The increased glutathione and catalase activity are indicative of the antioxidant properties ofC. nurvalastem bark extract. [ABSTRACT FROM AUTHOR]

Sugarcane nurseries raised from fluff were found to be infected with a deuteromycetous fungus namely Drechslera resulting in seedling blight. The causal organism was later identified as Drechslera state of Cochliobolus spicifer, The disease incidence varied from 10-30% and the seedling mortality ranged from 50-95%. Studies were conducted on isolation, symptomatology, etiology. varietal reaction, morphology and identification of the pathogen including some control aspects under laboratory conditions. Etiological studies revealed that there was 8-16% infection of the fluff obtained from different crosses and open pollination. Artificially infected seedlings exhibited the same symptoms that were observed on diseased seedlings under natural conditions. The seedling mortality under artificial inoculation varied from 85-100%. All the four sugarcane varieties tested for their reaction to artificial inoculation were observed to be susceptible but the degree of susceptibility varied. Among 10 chemicals tried for control dithane-M 45, thiride, brassicol, zineb and ziram proved the best in inhibiting more than 50% of the conidial germination and also the growth of the mycelium. Kasumin proved very poor in its fungitoxic property. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported autonomic dysfunction (AD) in multiple sclerosis (MS), bladder and/or bowel dysfunction, orthostatic hypotension, and cardiac adaptation disorders have been observed in a wide range (15-80%). The primary aim of this study is to investigate the frequency and association of AD in MS patients, assessed by sympathetic skin reaction (SSR) and a symptoms questionnaire. The secondary aims of this study are to study the association of AD and disease disability assessed by expanded disability status scale (EDSS), as well as disease duration. Design and Methods: 100 clinically definite MS patients were evaluated for ANS dysfunction by use of an autonomic symptoms questionnaire and SSR testing. The relationship between these methods, AD and disease-related parameters, such as the expanded disability status scale (EDSS) and disease duration were all evaluated. Results: 65% of the patients presented with AD and 29% of these patients had abnormal SSR results. MS patients with high EDSS values (EDSS >4) and longer disease duration were more likely to have ANS dysfunction (p less than 0.0001). Conclusions. ANS dysfunction is not uncommon in CDMS patients and thus noninvasive investigations of AD are warranted to optimize AD evaluation and disease management.

Obesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders.

Obesity remains a growing and global public health burden across a broad spectrum of metabolic, systemic, and neurodegenerative diseases. Previously considered merely a fat storage depot, adipose tissue is now recognized as an active endocrine organ crucial for metabolic and systemic regulation of local and distant organs. A burgeoning line of investigation centers on adipose-derived extracellular vesicles (ADEVs) and their pivotal role in obesity-associated pathobiology. However, robust methodologies are lacking for specifically isolating and characterizing human ADEVs. To bridge this gap, we have developed a robust multiparametric framework incorporating bulk and single EV characterization, proteomics, and mRNA phenotyping. EVs from matched human visceral adipose tissue, mature adipocyte-conditioned media, and plasma collected from the same individual bariatric surgical patients were analyzed and subjected to bottom-up proteomics analysis. This framework integrates bulk EV proteomics for cell-specific marker identification and subsequent single EV interrogation with single-particle interferometric reflectance imaging (SP-IRIS) and total internal reflection fluorescence (TIRF) microscopy. Our proteomics analysis revealed 76 unique proteins from adipose tissue-derived EVs (ATEVs), 512 unique proteins from adipocyte EVs (aEVs), and 1003 shared proteins. Prominent pathways enriched in ATEVs included lipid metabolism, extracellular matrix organization, and immune modulation, while aEVs exhibited enhanced roles in chromatin remodeling, oxidative stress responses, and metabolic regulation. Notably, adipose tissue-specific proteins such as adiponectin and perilipin were highly enriched in ADEVs and confirmed in circulating plasma EVs. Colocalization of key EV and adipocyte markers, including CD63 and PPARG, were validated in circulating plasma EVs. In summary, our study paves the way toward a tissue and cell-specific, multiparametric framework for an 'adiposity EV signature' in obesity-driven diseases.

Objective: To characterize how social adversities influence disease control in children with celiac disease (CeD)., Study Design: We conducted a cross-sectional analysis of data from 325 eligible children ≤18 years old with CeD enrolled between 2015 through 2023 into iCureCeliac, a patient-centered US registry for CeD. We evaluated the associations between financial insecurity, social stigmatization, decreased health knowledge, and mental health comorbidity with 2 validated patient-reported outcomes on disease activity and gluten-free diet adherence: celiac symptom index and CeD adherence test, respectively. We used multivariable logistic and linear regression analysis to adjust for race, primary spoken language, and socioeconomic status., Results: Among 325 children with available financial insecurity data, the median age was 11 years (IQR 8, 15), 67% were female, and 88% were White. In multivariable logistic regression, the odds of elevated disease activity among children with financial insecurity, social stigmatization, decreased health knowledge, and mental health comorbidity were 2.6 (95% CI 0.9, 8.0; P = .09), 2.8 (95% CI 1.6, 5.1; P < .001), 4.8 (95% CI 2.4, 9.8; P < .001), and 1.9 (95% CI 1.1, 3.3; P = .03), respectively. For insufficient dietary adherence, the respective odds were 1.6 (95% CI 0.5, 4.7; P = .43), 3.3 (95% CI 1.7, 6.5; P < .001), 2.9 (95% CI 1.5, 5.7; P = .002), and 2.3 (95% CI 1.2, 4.2; P = .01). Statistically significant associations in logistic regression aligned with results of linear models., Conclusions: Social stigmatization, decreased health knowledge, and mental health comorbidity were associated with worse disease control in pediatric CeD. Targeted interventions aimed at addressing these social adversities may improve disease activity and dietary adherence., Competing Interests: Declaration of Competing Interest All phases of this study were supported by NIH grants: T32DK007762 (T.C.) and K23DK132454 (S.I.W.). S.I.W. served on the Medical Advisory Board for Mirum Pharmaceuticals. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, it is developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of the coronavirus disease of 2019 (COVID-19). BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions. While GATA4-mediated ES-to-iXEN conversion was rapid and nearly deterministic, OCT4-, KLF4-, and SOX2-induced XEN-to-induced pluripotent stem (iPS) reprogramming progressed with diminished efficiency and kinetics. A dominant PrE transcriptional program, safeguarded by GATA4, alongside elevated chromatin accessibility and reduced DNA methylation of the EPI underscored the differential plasticities of the two states. Mapping in vitro to embryo trajectories tracked reprogramming cells in either direction along EPI and PrE in vivo states, without transitioning through the ICM., Competing Interests: Declaration of interests A.-K.H. is a member of the advisory board of Developmental Cell., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Schizophrenia is a chronic psychiatric disorder with a complex etiology involving genetic, neurobiological, and environmental factors. Many individuals with schizophrenia experience treatment resistance despite advances in pharmacologic and non-pharmacologic interventions. Immune dysregulation, characterized by altered cytokine levels, immune-related gene expression, and neuroinflammation, plays a critical role in schizophrenia's pathogenesis. Furthermore, associations between schizophrenia and bone marrow malignancies, with documentation of remission of treatment-resistant schizophrenia following bone marrow transplantation for malignancies, are emerging. This review synthesizes findings on the immunological underpinnings of schizophrenia, explores potential connections with bone marrow dysfunction, and evaluates the therapeutic potential of immune-modulating approaches, including bone marrow transplantation. By highlighting these connections, the study aims to advance understanding and stimulate prospective research into innovative treatments for this debilitating condition., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jayakumar et al.)

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals., (© 2024. The Author(s).)

Cell-state density characterizes the distribution of cells along phenotypic landscapes and is crucial for unraveling the mechanisms that drive diverse biological processes. Here, we present Mellon, an algorithm for estimation of cell-state densities from high-dimensional representations of single-cell data. We demonstrate Mellon's efficacy by dissecting the density landscape of differentiating systems, revealing a consistent pattern of high-density regions corresponding to major cell types intertwined with low-density, rare transitory states. We present evidence implicating enhancer priming and the activation of master regulators in emergence of these transitory states. Mellon offers the flexibility to perform temporal interpolation of time-series data, providing a detailed view of cell-state dynamics during developmental processes. Mellon facilitates density estimation across various single-cell data modalities, scaling linearly with the number of cells. Our work underscores the importance of cell-state density in understanding the differentiation processes, and the potential of Mellon to provide insights into mechanisms guiding biological trajectories., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Mucosal-associated invariant T (MAIT) cells have a semi-invariant T-cell receptor that allows recognition of antigen in the context of the MHC class I-related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1-restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon-gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL-17. Given that MAIT cells are present in human barrier tissues colonized by a microbiome, MAIT cells must somehow be able to distinguish colonization from infection to ensure effector functions are only elicited when necessary. Importantly, MAIT cells have additional functional properties, including the potential to contribute to restoring tissue homeostasis by expression of CTLA-4 and secretion of the cytokine IL-22. A recent study provided compelling data indicating that the range of human MAIT cell functional properties is explained by plasticity rather than distinct lineages. This further underscores the necessity to better understand how different signals regulate MAIT cell function. In this review, we highlight what is known in regards to activating and inhibitory signals for MAIT cells with a specific focus on signals relevant to healthy and inflamed tissues. We consider the quantity, quality, and the temporal order of these signals on MAIT cell function and discuss the current limitations of computational tools to extrapolate which signals are received by MAIT cells in human tissues. Using lessons learned from conventional CD8 T cells, we also discuss how TCR signals may integrate with cytokine signals in MAIT cells to elicit distinct functional states., (© 2024 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.)