A cross-sectional study on undernutrition among under-5 children living in the rural area of Hyderabad

Background: Undernutrition is a silent emergency and one of the most common causes of morbidity and mortality among under-5 children throughout the world. A serious public health concern and can have significant effect on child’s overall growth and development. The prevalence of undernutrition is two folds higher among rural area compared with urban area, therefore present study aims to study the prevalence of undernutrition and associated factors among under-5 children living in rural area of Hyderabad. Methods: A community based cross-sectional study was conducted between April 2023 to June 2023 in rural field practice area of a medical college in Hyderabad. A total of 364 under-5 children residing in study area were selected by simple random technique. Data about socio-demographic variables were collected by questionnaire and anthropometrics were measured using standard techniques. Results: In the present study, about 33% of under-5 children are underweight and 35% are stunted. The under-5 children belonged to lower socioeconomic class were significantly more likely to be underweight (40%) and stunted (42%). Family size >6 members were significantly underweight (48%) as well as stunted (47%). Children with low birth weight i.e. <2.5 kg had significantly higher rates of underweight (43%) as well as stunting (45%). Among the children with weaning age less than 6 months, 47% were underweight and 45.6% were stunted. Conclusions: Socio economic status, family size, birth weight, and weaning age are important determinants of undernutrition.

A rheumatological catastrophe: case of amyopathic juvenile dermatomyositis

Juvenile-onset amyopathic dermatomyositis is rare variant of juvenile-onset dermatomyositis (JDM), characterized by the hallmark cutaneous features of dermatomyositis without clinical or laboratory evidence of muscle disease. Dermatomyositis with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody has a distinct phenotype associated with small hand joint arthritis, mucocutaneous ulceration in the absence of muscle involvement. In this article, we describe a 5-year-old child presented with mucocutaneous manifestations with no muscle weakness who responded to immunosuppressive therapy.

Review on stroke induced depression

One of the frequent and dangerous aftereffects of stroke is post-stroke depression (PSD). About one in three stroke survivors had depression following their stroke. It had a significant impact on functional recovery, which resulted in a low standard of living. Even worse, there is a clear correlation between it and a high death rate. Our goal in doing this evaluation was to come up with a thorough and cohesive knowledge of PSD based on both recently released research and well-known works. We discovered that the incidence of PSD varies from 11 to 41% within a two-year period, based on a significant number of researches. The severity of the stroke, the location of the lesion, past history of depression, and other factors all has a role in the development of PSD. The DSM criteria are currently the primary basis for diagnosing PSD, and they are often coupled with different depression scales. However, there isn't a single, cohesive process that explains PSD which now include aberrant neurotrophic response, elevated inflammatory markers, lowered monoamine levels, glutamate-mediated excitotoxicity, and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Pharmacotherapy and psychosocial therapies are currently used in the treatment of PSD. Even though researchers have made significant progress, many problems still need to be solved. In particular, the PSD's mechanism is not entirely understood.

Histological and Endocrine Effects of Chronic Exposure to MP2.5 Derived from Wood Smoke in the Uterus of Nulliparous Adult Rats

SUMMARY: The study explores the relationship between chronic exposure to fine particulate matter (PM2.5), sourced from wood smoke, and the histological structure and endocrine function of the uterus in nulliparous adult rats. It assesses potential structural changes in the uterus that could impact reproductive health, viewing PM2.5 exposure as a possible risk factor. A controlled experiment was conducted in a city known for high air pollution levels, exposing rats to filtered and unfiltered air conditions, thus mimicking human PM2.5 exposure. Histological findings indicated a significant increase in collagen density and uterine wall thickness in PM2.5 exposed subjects, suggesting a reproductive function risk. However, no significant differences were observed in progesterone and estradiol hormone levels, pointing to the complex relationship between PM2.5 exposure and its endocrine impact, and emphasizing the need for further studies for a deeper understanding. This work highlights the importance of thoroughly investigating the long-term effects of PM2.5 pollution on reproductive health, underlining the significance of considering environmental exposure as a critical factor in reproductive health research.

El estudio explora la relación entre la exposición crónica a partículas finas (PM2,5), procedentes del humo de leña, y la estructura histológica y la función endocrina del útero en ratas adultas nulíparas. Evalúa posibles cambios estructurales en el útero que podrían afectar la salud reproductiva, considerando la exposición a PM2,5 como un posible factor de riesgo. Se llevó a cabo un experimento controlado en una ciudad conocida por sus altos niveles de contaminación del aire, exponiendo ratas a condiciones de aire filtrado y sin filtrar, imitando así la exposición humana a PM2,5. Los hallazgos histológicos indicaron un aumento significativo en la densidad del colágeno y el grosor de la pared uterina en sujetos expuestos a PM2,5, lo que sugiere un riesgo para la función reproductiva. Sin embargo, no se observaron diferencias significativas en los niveles de las hormonas progesterona y estradiol, lo que apunta a la compleja relación entre la exposición a PM2,5 y su impacto endocrino, y enfatiza la necesidad de realizar más estudios para una comprensión más profunda. Este trabajo destaca la importancia de investigar a fondo los efectos a largo plazo de la contaminación por PM2,5 en la salud reproductiva, subrayando la importancia de considerar la exposición ambiental como un factor crítico en la investigación de la salud reproductiva.

Under 5 pneumonia a forgotten pandemic: an insight into risk factors predicting outcome of severe pneumonia in children aged 2 months to 5 years of age

Background: Pneumonia is the leading cause of morbidity and mortality in the pediatric population. In developing countries like India, multiple sociodemographic and environmental factors influence the outcome of severe pneumonia so this study explores these risk factors with aim of finding ways to improve the outcome.Methods: It is a prospective observational study conducted over a period of 12 months on 2 months to 5 years, children with severe pneumonia admitted in ward and PICU of tertiary medical care institute. A total of 100 patients were enrolled in the given study after meeting the inclusion criteria. Predesigned proforma was used to record sociodemographic details, patient history, detailed examination findings and laboratory reports. Outcome in terms of mortality and morbidity was noted. Data analyzed using appropriate statistical tests, p values <0.05 accepted as statistically significant.Results: The severe pneumonia was more common in the age group of 2 months to 1 year of age (59%) and in males (60%). Malnutrition and leukocytosis was statistically significant. 53 subjects were exclusively breastfed. Type of family, mother & father抯 education status, mother抯 employment status, tobacco exposure and contact with tuberculosis were not found statistically significant in the given study. 21 participants required PICU and 10 patients required mechanical ventilation. 92 patients were discharged, while 2 patients expired.Conclusions: Pneumonia is an important preventable and treatable cause of under 5 mortalities. In developing countries like India an awareness and proper management of risk factors like malnutrition, low birth weight, immunization status can improve the outcome.

Uridine triacetate: the saviour in waiting, finally arrives

Cancer of the gastrointestinal tract is one of the very common solid cancers. Colorectal cancer is one of the types in which the anticancer drug 5-fluorouracil (5-FU) or its prodrug capecitabine is used. Toxicity to 5-FU or capecitabine is a common occurrence in patients receiving it. In such conditions, dose reduction or drug discontinuation for some time was the only way out apart from some supportive measures. An exhaustive search was always on to find a suitable antidote for the toxicity. The molecule uridine triacetate was studied for a long to be used in this condition. A systematic search of the existing literature about uridine triacetate was done with available sources like PubMed, Google Scholar, etc. Information about uridine triacetate was assembled and processed from these sources. Uridine triacetate was given orphan drug status for this indication a few years back. After a clinical trial, the drug was finally approved by the US FDA on December 11, 2015, for use in case of toxicity to 5- 5-FU or capecitabine. Well, stat Therapeutics has been marketing the drug under the trade name of Vistogard. Uridine triacetate works by preventing the toxic metabolite of 5-FU from entering and establishing itself in the RNA framework, by competing with the toxic metabolites. It is a relatively safe drug with minimal side effects. This article discusses the molecule uridine triacetate, its structure, metabolism, and kinetics in the body, the why and how of its action, and finally the results and findings of the clinical trial done with it.

Do statins decrease testosterone in men? Systematic review and meta-analysis

ABSTRACT Purpose: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. Materials and Methods: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. Results: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001). In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. Conclusion: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.

Dimensions of quality of life in patients with heart failure and sarcopenia: a scoping review protocol / Dimensões da qualidade de vida em pacientes com insuficiência cardíaca e sarcopenia: um protocolo de revisão de escopo

Objective: To map the dimensions of quality of life in patients with heart failure (HF) and sarcopenia. Methods: The scoping review will adhere to the JBI Manual for Evidence Synthesis methodology and will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Searches will encompass MEDLINE/PubMed, SCOPUS, EMBASE/Elsevier, LILACS, IBECS, BDENF (BVS), SciELO, Core Collection (Clarivate Analytics), CINAHL, Academic Search Premier (EBSCO), PsycINFO (APA), Cochrane Library, Epistemonikos, and academic search engines: Google Scholar and Bielefeld Academic Search Engine (BASE), without language or date restrictions. Inclusion criteria: Population ­ adults with HF and sarcopenia; Concept ­ Dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression ­ defined based on the EQ-5D-3L questionnaire; Context ­ any health care setting. Two independent reviewers will select studies and extract data, with a third reviewer consulted in cases of discrepancies. Findings will be presented graphically with a narrative summary. Expected results: We aim to uncover key dimensions of quality of life in individuals with HF and sarcopenia through this scoping review. Anticipated outcomes include insights into mobility, self-care, usual activities, pain/discomfort, and anxiety/depression across diverse health care settings. Relevance: This review sheds light on the interplay between HF and sarcopenia and its impact on quality of life. The findings may guide interventions, inform evidence-based decision-making, and contribute to targeted strategies to improve the wellbeing of individuals managing both conditions. Review registration: Open Science Framework [https://archive.org/details/osf-registrations-jn387-v1]. (AU)

Papel da Rigidez Aórtica na Previsão da Resposta aos Inibidores da Fosfodiesterase-5 no Tratamento da Disfunção Erétil / Role of Aortic Stiffness in Predicting Response to Phosphodiesterase-5 Inhibitors in the Treatment of Erectile Dysfunction

Resumo Fundamento: Sabe-se que a rigidez aórtica (RA) aumenta em pacientes com disfunção erétil (DE). Os inibidores da enzima fosfodiesterase tipo 5 (PDE-5) são usados no tratamento da DE, e as respostas dos pacientes a esse tratamento podem variar. Objetivos: Nosso objetivo foi investigar o papel da RA na previsão da resposta de pacientes planejados para tomar inibidores da enzima PDE-5 devido à DE. Métodos: Um total de 96 pacientes do sexo masculino com DE foram incluídos no estudo. O questionário do Índice Internacional de Função Erétil (IIEF) foi utilizado para avaliar a presença e gravidade da DE e a resposta ao tratamento. A ecocardiografia transtorácica foi utilizada para avaliar RA. Resultados: Houve diferença estatisticamente significativa entre os valores de deformação aórtica e distensibilidade aórtica dos grupos de estudo (p<0,001). O escore delta IIEF apresentou alto nível de correlação positiva com a deformação aórtica (p<0,01, r=0,758) e um nível moderado de correlação positiva com a distensibilidade aórtica (p<0,01, r=0,574). Conclusão: Determinamos que em pacientes com DE, a deformação aórtica e a distensibilidade aórtica medidas de forma não invasiva por meio de ecocardiografia transtorácica são parâmetros importantes na previsão da resposta dos pacientes à terapia com inibidores da PDE-5.

Abstract Background: It is known that aortic stiffness (AS) increases in patients with erectile dysfunction (ED). Phosphodiesterase type-5 (PDE-5) enzyme inhibitors are used in the treatment of ED, and patients' responses to this treatment may vary. Objectives: We aimed to investigate the role of AS in predicting the response of patients planned to take PDE-5 enzyme inhibitors due to ED. Methods: A total of 96 male patients with ED were included in the study. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate the presence and severity of ED and the response to treatment. Transthoracic echocardiography was used to evaluate AS. Results: There was a statistically significant difference between the aortic strain and aortic distensibility values of the study groups (p<0.001). The delta IIEF score had a high level of positive correlation with aortic strain (p<0.01, r=0.758) and a moderate level of positive correlation with aortic distensibility (p<0.01, r=0.574). Conclusion: We determined that in patients with ED, aortic strain and aortic distensibility measured non-invasively using transthoracic echocardiography are important parameters in predicting patients' response to PDE-5 inhibitor therapy.

Ethics and Welfare in invertebrates: a stepping-stone to research and animal production / Ética y bienestar en invertebrados: una piedra fundamental en investigación y producción animal

Abstract Introduction: Even though only a few species are considered to be dangerous, pests or vectors, the majority of invertebrates produce a feeling of aversion in humans. This has contributed to the delay in the development of ethical considerations as regards this group in contrast with vertebrates, with the exception of cephalopods. Objective: In the present study, we provide an overview of the current situation on animal ethics and welfare in order to contribute to the development of a framework for ensuring invertebrate welfare. Methods: Today, animal welfare is multidisciplinary in nature to a very high degree as it includes ethology, physiology, pathology, biochemistry, genetics, immunology, nutrition, cognitive-neural, veterinary medicine, and ethics. Animal welfare is a complex concept, difficult to achieve successfully from one perspective. Results: As a consequence, we propose to include the five domains (nutrition, environment, health, behaviour and mental state) along with the three conceptions (basic health and functioning, affective state and natural living), as well as the 5R Principle (Replace, Reduction, Refinement, Respect and Responsibility) in seeking to achieve a comprehensive welfare state. Conclusions: We consider that in both research and animal production, the individual and collective ethical concerns coexist and, in fact, the main moral concern to account for is the collective one and that, within that collective view, the individual moral concern should be applied with responsibility and respect for the individual. Finally, we propose a practical example of invertebrate welfare production in sea urchin aquaculture with the aim of including animal production of invertebrates in this important discussion.

Resumen Introducción: Aunque sólo unas pocas especies son consideradas peligrosas, plagas o vectores, la mayoría de los invertebrados producen un sentimiento de aversión en el ser humano. Esto ha contribuido al retraso en el desarrollo de consideraciones éticas respecto a este grupo en comparación con los vertebrados, a excepción de los cefalópodos. Objetivo: En el presente trabajo, proporcionamos una visión general de la situación actual en materia de ética y bienestar animal con el fin de contribuir al desarrollo de un marco para garantizar el bienestar de los invertebrados. Métodos: Hoy en día, el bienestar animal es de naturaleza multidisciplinaria en un grado muy alto, ya que incluye etología, fisiología, patología, bioquímica, genética, inmunología, nutrición, cognitivo-neural, medicina veterinaria y ética. El bienestar animal es un concepto complejo, difícil de lograr con éxito desde una sola perspectiva. Resultados: Como consecuencia, proponemos incluir los cinco dominios (nutrición, ambiente, salud, comportamiento y estado mental) junto con las tres concepciones (Salud básica y funcionamiento, estado afectivo y vida natural), así como el Principio 5R (Reemplazar, Reducir, Refinar, Respetar y Responsabilidad) en la búsqueda de alcanzar un estado de bienestar integral. Conclusiones: Consideramos que tanto en la investigación como en la producción animal coexisten las preocupaciones éticas individuales y colectivas y, de hecho, la principal preocupación moral a dar cuenta es la colectiva y que, dentro de esa visión colectiva, se debe aplicar la preocupación moral individual. con responsabilidad y respeto por la persona. Finalmente, proponemos un ejemplo práctico de producción de bienestar de invertebrados en la acuicultura de erizos de mar con el objetivo de incluir la producción animal de invertebrados en esta importante discusión.

Metabolite profiling and in-vitro evaluation of cytotoxic efficacy of Psychotria dalzellii Hook.f. on MCF-7 and L929 cell lines

In the current study Psychotria dalzellii Hook.f. stem-bark samples were procured from Joida, Western Ghats, Karnataka, India. air-dried and subjected to Soxhlet extraction. The obtained extracts were screened for preliminary phytochemicals which resulted in the existence of flavonoids, alkaloids, glycosides, phenols, tannins, steroids, triterpenoids, saponins, carbohydrates and lignins. Subsequently, the ethanolic stem bark extracts were subjected to GC-MS analysis to quantitatively estimate the phytoconstituents. It reveals the presence of 20 bioactive chemicals. Among them, 2-Furancarboxaldehyde, 5-(hydroxymethyl)- (59.26%); p-Mesyloxyphenol (10.68%); 2-Furaldehyde diethyl acetal (4.54%); 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl (4.11%) were noted to be the principal compounds detected. Furthermore, in-vitro cytotoxic activities on MCF-7 and L929 cell lines were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. The extract exhibited considerable cytotoxic activity towards MCF-7 cell lines at higher concentrations with an IC50 value of 440.82 µg/ml and it showed very less toxicity towards L929 normal cell lines. Which indicates its potential as a possible source of bioactive constituents for medicinal and pharmaceutical exploration.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Espondiloencondrodisplasia con desregulación inmune relacionada a ACP5. Reporte de cuatro casos / Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases

La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.

FNDC5/Irisin in dementia and cognitive impairment: update and novel perspective

Epidemiological surveys show that the incidence of age-related dementia and cognitive impairment is increasing and it has been a heavy burden for society, families, and healthcare systems, making the preservation of cognitive function in an increasingly aging population a major challenge. Exercise is beneficial for brain health, and FDNC5/irisin, a new exercise-induced myokine, is thought to be a beneficial mediator to cognitive function and plays an important role in the crosstalk between skeletal muscle and brain. This review provides a critical assessment of the recent progress in both fundamental and clinical research of FDNC5/irisin in dementia and cognitive impairment-related disorders. Furthermore, we present a novel perspective on the therapeutic effectiveness of FDNC5/irisin in alleviating these conditions.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

SNORA5A regulates tumor-associated macrophage M1/M2 phenotypes via TRAF3IP3 in breast cancer

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

Antitumor and cytotoxic potential of various extracts of Gloriosa superba L. Centaurea behen L., Elaeocarpus ganitrus Roxb and Ficus religiosa L. against human breast cancer (MDA-MB 231) cell lines

Background: Medicinal plants are rich in a wide variety of secondary metabolites such as tannins, alkaloids, phenolic compounds, flavonoids etc. which have the capability to inhibit many pathways that lead to cancer. The present study was conducted with the objectives to screen the extracts of dried roots Gloriosa superba L., dried roots of Centaurea behen L. dried fruits/beads of Elaeocarpus ganitrus Roxb., dried leaves of Ficus religiosa L. and investigate their antitumor activity on human breast cancer cell lines (MDA-MB 231). Methods: Cytotoxic activity was evaluated against non-cancerous cell lines (MCF-10A). Hexane, chloroform, methanol and water were the solvents used for extraction of phytoconstituents by Soxhlet method. Anti-proliferative potential of the plant extracts was evaluated using MTT assay. The trypan blue dye exclusion test was used to determine the number of viable cells present in a cell suspension. Results: On MDA MB-231 cell lines, 91.94% cell death was reported with G. superba aqueous extract followed by E. ganitrus methanol extract and F. religiosa hexane extract with 87.93% and 81.61% cell death respectively. Moreover, none of the extracts had shown cytotoxic effect while evaluated against normal non-cancerous cell lines (MCF- 10A). Conclusions: It is inferred from the current findings that phytoconstituents present in the plant extracts have high anticancer potential. These phytoconstituents along with some new anticancer agents present in the plant extracts reflects the high cytotoxic potential against cancer cells.

Mechanism of HMGB1 in scarring after glaucoma drainage valve implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the dynamic expression of high mobility group box 1(HMGB1)in scar tissues after glaucoma drainage valve implantation, and to further reveal the role and possible mechanism of HMGB1 in scarring after glaucoma surgery.METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group(n=20), model group(n=20, silicone implantation under conjunctival sac)and model with drug administration group(n=20, silicone implantation under conjunctival sac combined with 5-fluorouracil injection). The conjunctival tissues were collected at 4 and 8 wk after surgery. HE staining and Masson staining were used to detect the proliferation and distribution of fibroblasts and collagen fibers in conjunctival tissues. Immunohistochemistry was utilized to detect the distribution and changes of HMGB1, transforming growth factor(TGF)-β1, Smad3 and α-smooth muscle actin(SMA)in conjunctival tissues. RT-PCR and Western blot were adopted to detect the mRNA and protein expression of HMGB1, TGF-β1, Smad3 and α-SMA in conjunctival tissues.RESULTS: HE staining and Masson staining showed that the proliferation of inflammatory cells, fibroblasts and collagen fibers in the model group was significantly higher than that in the control group at both 4 and 8 wk. Meanwhile, the proliferation of fibroblasts and collagen fibers in the model with drug administration group was significantly lower than that in the model group. Immunohistochemical staining showed that the expression of HMGB1, TGF-β1, Smad3 and α-SMA protein was observed in the conjunctival tissues of the model group both 4 and 8 wk, with brown and significantly deeper staining of the model group at 8 wk. Meanwhile, the positive staining in the model with drug administration group at both 4 and 8 wk was significantly lower than that in the model group. There was positive correlations between the number of fibroblasts stained with HE and the expression of HMGB1 in the conjunctival tissue of the model group at both 4 and 8 wk(r=0.602, 0.703, all P&#x0026;#x003C;0.05). RT-PCR and Western blot revealed that the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model group were significantly higher than those in the control group at both 4 and 8 wk(all P&#x0026;#x003C;0.05). Meanwhile, the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model with drug administration group were significantly lower than those in the model group(all P&#x0026;#x003C;0.05). There was positive correlations between mRNA expressions of HMGB1 and TGF-β1, Smad3 in the model group and the model with drug administration group(all P&#x0026;#x003C;0.05).CONCLUSION: The expression of HMGB1 increased at a time-dependent manner after glaucoma valve implantation. HMGB1 acts an indispensable role in the initiation and progression of scar formation after glaucoma surgery, which may be involved in the regulation of TGF-β/Smad signaling pathway.