Phytochemical characterization by GC-MS and in vitro evaluation of antiproliferative and antimigratory studies of Leucas aspera leaf extracts on MDA-MB-231 cell line.

Breast cancer is the most recurrently identified and one of women's prominent causes of death. Currently, researchers have turned their focus on natural chemicals from synthetic chemicals due to their environmental, economic, and health benefits. Considering this, the medicinal plant Leucas aspera was chosen for the current study. The aim of this study was to isolate and characterize secondary metabolites from L. aspera and determine the antiproliferative and antimigratory activities in the MDA-MB-231 cell line under in vitro conditions. Phytochemicals from L. aspera were isolated through sequential extraction using hexane, dichloromethane, and ethyl acetate. These extracts were qualitatively screened, subjected to FT-IR, and analyzed using GC-MS. The antiproliferative activity was determined through the MTT assay. Scratch assay was utilized to determine the antimigratory activity of the plant extracts. The phytochemical analysis revealed the presence of steroids, alkaloids, phenols, flavonoids, galactose, tannins, saponins, and amino acids in the extracts. The results of the cell viability assay indicated that the crude dichloromethane and ethyl acetate extracts inhibited cell proliferation, with inhibitory concentrations of 5 and 3 µg/ml, respectively. In contrast, the crude hexane extract did not exhibit any cytotoxicity. Furthermore, the scratch assay results showed that the plant extracts had cell migration inhibitory properties. The outcomes of the current study conclude that L. aspera possesses active therapeutic agents with strong anticancer potential, effectively impeding the proliferation and invasion of MDA-MB-231. Further studies are needed to identify the potential active agents that contribute to these activities.

Environmental enteric dysfunction and small intestinal histomorphology of stunted children in Bangladesh.

There is lack of information on the histological characteristics of the intestinal mucosa in Bangladeshi children. Collection of intestinal biopsy samples and assessment of the histomorphological features is considered to be the traditional gold standard for diagnosis of environmental enteric dysfunction (EED). The purpose of the study was to evaluate the intestinal histological characteristics of stunted children aged between 12-18 months with possible EED. 110 children with chronic malnutrition (52 stunted with length-for-age Z score, LAZ<-2 and 58 at risk of stunting with LAZ <-1 to -2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study protocol who underwent upper gastrointestinal (GI) endoscopy were selected for this study. To explore the association of EED with childhood stunting, upper GI endoscopy was done and the biopsy specimens were studied for histopathology. Villous height and crypt depth were measured and the presence and intensity of inflammatory infiltrates in the lamina propria was investigated. Bivariate analysis was performed to examine the relationship between stunting and histologic morphology. More than 90% children irrespective of nutritional status were diagnosed to have chronic non-specific duodenitis on histopathology. Half of the children from both groups had villous atrophy as well as crypt hyperplasia and lymphocytic infiltration was present in more than 90% children, irrespective of groups. However, no statistically significant difference was observed when compared between the groups. The prevalence of chronic non-specific duodenitis in Bangladeshi children, irrespective of nutritional status, was high. A significant number of these children had abnormal findings in intestinal histomorphology. Trial registration number: ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016. https://clinicaltrials.gov/ct2/results?cond=NCT02812615&term=&cntry=&state=&city=&dist.

Gelidiella acerosa Compounds Target NFκB Cascade in Lung Adenocarcinoma.

In carcinogenesis, increased metabolism, abnormal functioning of mitochondria, peroxisomes, aberrant cell signaling, and prolonged inflammation can result in the overproduction of reactive oxygen species (ROS). In turn, excess ROS can upregulate the expression of various signaling pathways including the MAP kinase, PI3K/Akt, and NFκB cascades in cancer. The constitutive expression of NFκB causes drug resistance in lung cancer. Hence, drugs that can enhance the antioxidant activity of enzymes and regulate the NFκB activity are of prime target to manage the drug resistance and inflammation in cancer. This study evaluated the effect of compounds present in ethyl acetate extract of Gelidiella acerosa on inflammation and on antioxidant enzymes in lung cancer. The anti-inflammatory activity was determined under in silico and in vitro conditions. The in silico analysis showed that the phyto-constituents of G. acerosa inhibit the IKBα-NFκB-p65-p50 complex in a similar way as that of doxorubicin and dexamethasone. Similarly, G. acerosa treatment enhanced the efficiency of antioxidant enzymes peroxidases and superoxide dismutase in A549 lung cancer cells. Furthermore, the results of in vitro analysis showed that G. acerosa can decrease the activation of NFκB and production of pro-inflammatory cytokines and upregulate the expression of IL 10. As inflammation causes cancer progression, the inhibition of inflammation inhibits tumorigenesis. Hence, based on the results of the study, it can be concluded that G. acerosa exerts anti-inflammatory activity by decreasing the expression of NFκB cascade and moreover, the phyto-constituents of G. acerosa may have the potential to regulate the inflammatory response.

Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.

Alterations in the histological features of the intestinal mucosa in malnourished adults of Bangladesh.

There is paucity of knowledge on the histological features of the intestinal mucosa in malnourished adults of Bangladesh. The purpose of the study was to explore the histological features of the intestinal mucosa in malnourished adults of Bangladesh and to compare the findings with their well-nourished counterparts. 64 adults (37 malnourished with body mass index, BMI < 18.5 kg/m2 and 27 controls with BMI > 18.5 kg/m2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study, who underwent upper-gastrointestinal endoscopy, were selected for this study. With a view to address the association of environmental enteric dysfunction (EED) with malnutrition, upper-gastrointestinal endoscopy was performed and mucosal biopsies from the distal duodenum were studied for histopathology. Villous height, crypt depth, and presence of inflammatory infiltrates in lamina propria were investigated. Bivariate analysis was performed to quantify the relation between malnutrition and the histological features. About 95% adults, irrespective of nutritional status, were diagnosed to have chronic non-specific duodenitis on histopathology. Malnourished adults suffered significantly more from chronic active duodenitis compared to their well-nourished counterparts (p = 0.003). Malnourished adults also had significantly higher frequency of subtotal villous atrophy, crypt hyperplasia and marked cellular infiltration in the lamina propria than the healthy controls (p < 0.05).

Asymptomatic Duodenitis and Helicobacter pylori associated Dyspepsia in 2-Year-Old Chronic Malnourished Bangladeshi Slum-Dwelling Children: A Cross-Sectional Study.

AIM: There is insufficient knowledge on the * duodenal histology and Helicobacter pylori infection in malnourished Bangladeshi children. Therefore, we attempted to explore the prevalence of H. pylori infection and duodenal histopathology in 2-year-old chronic malnourished Bangladeshi slum-dwelling children and investigate their association with dyspeptic symptoms. METHODS: This cross-sectional study was conducted using the data of the Bangladesh Environmental Enteric Dysfunction study in an urban slum of Dhaka, Bangladesh. With a view to address the association of environmental enteric dysfunction (EED) with stunting, upper gastrointestinal endoscopy was performed on 54 chronic malnourished children {31 stunted [length-for-age Z-scores (LAZ) <-2] and 23 at risk of stunting (LAZ <-1 to -2)} aged between 12-24 months and the mucosal biopsies were subjected to histopathological examination after obtaining proper clinical history. Stool antigen for H. pylori (HpSA) was assessed to determine H. pylori status. RESULTS: In all, 83.3% (45/54) of the children had histopathological evidence of duodenitis. Chronic mild duodenitis was found to be the most prevalent form of duodenitis (53.7%) in the children. Only 8.9% (4/45) of the children with duodenitis had dyspepsia (p < 0.05). The 14.8% (8/54) of the children were found positive for H. pylori infection. Logistic regression analysis revealed children positive for HpSA had significant association with dyspepsia (OR 9.34; 95% CI 1.54-56.80). CONCLUSIONS: The number of chronic malnourished children suffering from duodenitis was found to be very high. Majority of these children was asymptomatic. Children positive for HpSA had significant association with dyspeptic symptoms.

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).

Nodal combined blue nevus and benign nevus cells in multiple axillary sentinel nodes in a patient with breast carcinoma: report of a case.

Combined blue nevus and benign nevus cells were identified in the same sentinel lymph node. Blue nevus alone was also present in an additional sentinel lymph node in the same axilla in a patient who underwent needle localization, wide local excision, and sentinel lymph node biopsy for her pT1cN1mi(sn)M(na) invasive duct carcinoma of the breast. Of the 4 sentinel lymph nodes, 1 showed micrometastasis and 2 other lymph nodes showed blue nevus involving the capsule and trabeculae of the nodes. The patient had no significant previous clinical history of any skin tumors and had a negative clinical examination for malignant melanoma or pigmented skin lesions after the diagnosis of nodal blue nevus. To our knowledge, this is the first case report of combined blue nevi involving multiple sentinel lymph nodes in the same axilla. An equally interesting finding is the presence of benign nonpigmented nevus cells in continuation with the blue nevus in the same node.

Unusual nonrefractile eosinophilic crystal in breast ducts in a patient with invasive mucinous carcinoma.

A 72-year-old, G4P2 white woman presented with a recent abnormal mammogram showing a nodule at 8 o'clock of her right breast and indeterminate calcification in the subareolar region. An initial stereotactic core followed by wide local excision and sentinel node biopsy showed a pT1aN0(sn)M(na) low-grade invasive mucinous carcinoma. In dilated benign ducts, adjacent to the carcinoma, numerous eosinophilic, nonrefractile crystals were identified.

Mucin extravasation in breast core biopsies--clinical significance and outcome correlation.

AIMS: To document the spectrum of lesions associated with mucin extravasation (ME) in breast core biopsy specimens, and to correlate with open surgical excisions. METHODS AND RESULTS: Thirty-nine lesions in 37 women with ME on core biopsies constituted the study group. Fibrocystic change (FC), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were found in 21 (53.8%), 13 (33.3%) and four (10.3%) core biopsy specimens, respectively, with one (2.6%) consisting only of mucin pools. Except for the latter, all disclosed mucocoele-like lesions (MLL) accompanying ME. Columnar cell lesions (CCL) were frequently observed (84.6%). On open biopsy, three cases underdiagnosed on core biopsy included FC that later disclosed ADH; one ADH lesion on core later upgraded to DCIS; and a case of mucin pools that revealed mucinous carcinoma on excision. The extent of CCL on core biopsy appeared to predict sinister lesions on open excision. For calcified lesions that were completely removed on core biopsy, there were no malignant lesions discovered on open excision that had not already been diagnosed preoperatively. CONCLUSIONS: ME and MLL on core biopsy warrant close radiological-pathological correlation. When the entire radiological abnormality has been removed with large core mammotome biopsy specimens, surgery may potentially be avoided in histologically benign lesions, although such an approach requires further validation.

Effects of the advent of disease on smoking habit.

PIP: A study was undertaken to determine the effect of the development or disease on patients' smoking habits. Interviews with 841 subjects (591 smokers) were conducted following a standard protocol. Of the 841 subjects, 96 (61 smokers) had hydroceles or hernias and were considered a control group; the remainder had neoplastic diseases, respiratory disorders, diabetes, cardiovascular diseases, psychiatric illnesses, peripheral vascular diseases, and gastrointestinal and liver disorders. Patients with cardiovascular, pulmonary, and neoplastic diseases, diabetes, gastrointestinal diseases, and cirrhosis of the liver significantly reduced or stopped smoking because of medical advice (19%), socioeconomic factors (8%), or aggravation of disease (24%). The advent of disease was associated with an increase in smoking in several patients (including 2 with bronchial asthma and 12 with peripheral vascular disease) because of the apparent belief that smoking is beneficial in overcoming the disease or in controlling pain. Additional long-term studies are needed to explore the relationship between disease and smoking habits.^ieng