Interlinked switch circuits of biological intelligence.

Eukaryotic cells learn and adapt via unknown network architectures. Recent work demonstrated a circuit of two GTPases used by cells to overcome growth factor scarcity, encouraging our view that artificial and biological intelligence share strikingly similar design principles and that cells function as deep reinforcement learning (RL) agents in uncertain environments.

Extralobar Pulmonary Sequestration in Adrenal Mimicking Neuroblastoma: A Case Report.

Background: Extralobar pulmonary sequestration (ELS) is a malformation composed of bronchopulmonary tissue outside the lungs that is discontinuous from the main tracheobronchial tree. ELS can present as a suprarenal space occupying lesion. Case Report: A 1-day old girl presented with a right supra-adrenal mass, first detected in-utero at 34 weeks. The differential included congenital neuroblastoma, but the urinary VMA was normal. At resection, there was lung tissue composed of dilated and tortuous bronchioles lined by columnar epithelium present in a back- to- back arrangement along with thick-walled vessels, features of an ELS with congenital pulmonary airway malformation type II. Conclusion: ELS enters the differential diagnosis of neonatal suprarenal masses with normal urinary catecholamines, and can have the morphology of a type II congenital pulmonary airway malformation.

Yolk Sac Tumour Arising in the Glans Penis an Achondroplasic Child: A Case Report with Summary of Prior Published Cases.

BACKGROUND: Yolk sac tumors (YST) are commonly encountered gonadal germ cell tumors in children, especially in the prepubertal age group. In addition to gonadal primary, it can occur in multiple extragonadal sites, of which sacrococcygeal, retroperitoneum, gastric and mediastinum are the commonest. There are 4 previous reports of primary penile YST. CASE REPORT: We describe a primary penile yolk sac tumor in a child with achondroplasia. CONCLUSION: Yolk sac tumor can occur in the penis during the prepubertal period. Penile yolk sac tumor associated with achondroplasia has not been previously reported, but this could be incidental.

Labial Lipoblastoma in an Infant: An Uncommon Tumor at an Uncommon Site.

Lipoblastoma and lipoblastomatosis are benign fatty tumors of soft tissues that are unique to childhood. Occurrence of lipoblastoma in the labial region is infrequent and can cause diagnostic dilemma. Awareness about this entity is important to avoid hazardous treatment in young children. Here, we present a case of labial lipoblastoma in a 2-year-old child along with its differential diagnosis.

Biliary atresia with splenic malformation with associated ductal plate malformation and duodenal atresia: A case report.

ABSTRACT: Biliary atresia (BA) is the most common cause of the obstructive type of neonatal cholestasis that requires prompt surgical intervention. About 10% of neonates with BA have other congenital anomalies, of which splenic malformation (BASM) is a well-known distinct sub-group. There is sparse literature on the association of duodenal atresia and ductal plate malformation (DPM) in patients of BASM. We describe a BASM associated with DPM and duodenal atresia in a 35-day-old infant, who succumbed at 40 days, before portoenterostomy could be performed. Duodenal atresia can be one of the associated malformations associated with BASM and ductal plate abnormalities. In our case, the child did not survive.

Small Molecular Antimicrobial Ligands of YspD are Potential Therapeutic Agents Against Yersinia enterocolitica Infection.

YspD is a hydrophilic translocator forming the platform for assemblage of functional translocon. Exposure to the extra-cellular milieu makes YspD a potential therapeutic target. DoGSiteScorer predicted best druggable pocket (P0) within YspD, encompassing predominantly the C-terminal helical bundles and the long helices-9 & 5. COACH metaserver also identified ligand binding residues within the aforementioned druggable pocket mapping to helix-9. Amino acids of helix-9 are involved in oligomerization of YspD. Interaction of helix-9 and parts of C-terminal of YspD with hydrophobic translocator protein (YspB), is essential for translocation of bacterial effectors to initiate an infection. Helices-9 & 5 form an intramolecular coiled-coil structure, required for protein-protein interaction. Targeting intramolecular coiled-coil and parts of C-terminal would be important for functional inactivation of YspD. Solvent exposed surface in YspD, particularly in P0, enhances its accessibility to ligands. Nine small molecular inhibitors of TIIISS were identified and retrieved from ZINC15 database (drug-library) as putative drug candidates. Molecular docking of potential ligands with P0 was done using SwissDock server and Achilles Blind Docking server. Considering the "Significance" threshold of binding score and region of interaction, Salicylidene Acyl Hydrazide derivatives (INP0400) and Phenoxyacetamide derivative (MBX1641) were found to bind effectively with YspD. These potential ligands interact with functional domains of YspD including parts of C-terminal and the intramolecular coiled-coil, which may affect the oligomerization of YspD and disrupt the interaction of YspD with YspB, inhibiting formation of functional translocon. The identified small molecular antimicrobial ligands of YspD could be tested in vivo to attenuate Y. enterocolitica infection by deregulation of Ysa-Ysp TIIISS. Supplementary Information: The online version contains supplementary material available at 10.1007/s40011-022-01443-2.

Effects of starch-rich or fat-rich diets on metabolism, adiposity, and glycemia in immune-biased, C57BL/6 and BALB/c mice.

Diet maintains health by regulating host metabolism and immunity. The results revealed the consequence of starch-, unsaturated fat-, and saturated fat-rich diets on differentially immune-biased mice C57BL/6 and BALB/c. Time-course of various diets on differentially immune-biased mice revealed that starch-rich and unsaturated fat-rich diets reduced insulin resistance (IR) and visceral adiposity in BALB/c mice while a saturated fat-rich diet enhanced both parameters. In C57BL/6 mice, a fat-rich diet enhanced IR with time while visceral adiposity remained unchanged. Eight weeks' consumption of saturated fat-rich diet induced highest visceral adiposity in C57BL/6 mice, while the same diet resulted in the maximum IR in BALB/c mice. The current report presented a detailed metabolomic analysis of diets and evaluated differential index of each treatment for each mouse strain using a vector analysis of the multivariate linear discriminant data. The outcome identified metabolites that affected lipid and glucose metabolism to establish the inter-strain physiological differences.

Effects of two potential probiotic Lactobacillus bacteria on adipogenesis in vitro.

AIMS: Overweight is a major global health problem. Various methodologies to get rid of the extra fat are available, but usually, those are associated with adverse side effects. Probiotics, on the contrary, seem to have the potential to help reduce fat accumulation without much apparent adversity. In this study, we have evaluated a pair of well-documented probiotics for their anti-obesogenic effects. MAIN METHODS: We used strains of Lactobacillus acidophilus (LA) and a cocktail (LDB-ST) of Lactobacillus delbruckei sp. bulgaricus (LDB) and Streptococcus thermophilus (ST) in this study. The murine pre-adipocyte cell line 3T3-L1 was terminally differentiated to matured adipocytes to use as a model to evaluate the bacteria's anti-obesogenic effects. The optimal dose for treatment of both the probiotics was determined using a cell viability assay. We assessed the probiotic internalization potential of differentiated 3T3-L1 cells by flow cytometry, fluorescence microscopy, and cell lysis method. We determined the lipolytic and anti-adipogenic potential of probiotics by intracellular lipid staining, spectrophotometry, and gene expression analysis. KEY FINDINGS: Both probiotics were effective lipolytic agents as revealed by reducing cellular lipids and down-regulation of mammalian adipogenesis marker genes in terminally differentiated 3T3-L1 cells. SIGNIFICANCE: Previous studies from our group had proven the immune-modulatory properties of these probiotics on an immune-biased mouse model. The present study demonstrates LA and LDB-ST to be effective against adipogenesis. Further in vivo studies will be conducted to strengthen this claim.

Endocrine Disruptors-'Food' for Thought.

Green vegetables, fruits, cereals, and pulses are all rich sources of antioxidants. Retinoic acid, ascorbate, proanthocyanidins, tannins, saponins, melatonin, curcumin, allicin, and alpha-lipoic acid stand documented in plants as bioactive compounds. The international dietary committee advocates a specific quantum of these natural antioxidants through diet. Interestingly, environmental pollution has indeed affected most of these farm products. The use of chemical fertilizers, pesticides and heavy metals in soil has a cumulative effect on human health. Enough evidence is available for the presence of phytoestrogen, xenoestrogen, and a host of other endocrine disruptors in the food. These plant-based nutrients can mimic or enhance the natural hormone's health effects. While endocrine disruptors are found in many everyday products, this review aims to address endocrine disruptors from food in the Asian subcontinent. 'Food for thought' justifies the paradigm shift towards good endocrine health by swaying away from the conventional daily dietary recommendations.

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management.

Diabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes.

Macrophage plays important role in cortisol and serotonin induced adipogenesis in vitro.

Psychological stress is an important cause to induce various metabolic disorders such as obesity, type II diabetes, and cardiovascular disorders by affecting the visceral adipose tissue. Pathophysiology of these diseases is often accompanied by the hyperactive immune system. The hyperactive immune system causes immune cells to infiltrate in the adipose tissue to increase the severity of metabolic disorders and to affect the levels of stress associated hormones, such as cortisol and serotonin. Cortisol and serotonin, alone or together, could regulate several aspects of the metabolic and immunological deregulations by manipulating the lipid accumulation or adipogenesis in cells. During adipogenesis, macrophages are recruited. Previous reports from the Aich laboratory established the roles of cortisol and serotonin to influence adipogenesis in pre-adipocytes 3T3-L1 in the presence and absence of macrophages. In the current study, we reported the role of macrophage RAW264.7, especially its polarized states, on differentiated murine adipocytes 3T3-L1 in the presence or absence of cortisol and serotonin. The current study also compares the differential role of macrophage recruitment on pre- and differentiated adipocytes.

Lactobacillus rhamnosus GG reverses mortality of neonatal mice against Salmonella challenge.

Pathogenic infection is one of the major causes of death in newborns. Antibiotic based therapies are still the major mode of treatment for infection. Increased usage of antibiotics leads to selective evolution of microorganisms and causes diseases in adulthood. Attempts to develop alternatives to antibiotics did not yield much success. A recent viable trend is to identify novel probiotics that could alleviate problems associated with over usage of antibiotics. We screened three different Lactobacillus species to establish their efficacy in neonates in protecting against Salmonella challenge. The methodologies employed are metagenomics, metabonomics, transcriptional profiling, molecular assays and behavioral studies. Among the three probiotics used, only Lactobacillus rhamnosus GG (LGG) treatment of the neonates resulted in rescuing of 80% of the Salmonella-infected mice. We have shown that LGG (MTCC #1408) can prevent Salmonella mediated infection in neonates. In the current report, results from histopathology, gene expression, neutrophil infiltration, metabolite and metataxonomic profiling, and protein level data suggested that LGG treatment of the neonates enhanced anti-inflammatory cytokine expression and increased the gut barrier function. The current report establishes the potential use of LGG in clinical intervention of infectious diseases.

Melatonin protects against chromium (VI) induced hepatic oxidative stress and toxicity: Duration dependent study with realistic dosage.

The present study was undertaken to assess the degree of oxidative stress and toxic effects induced by chromium on hepatic tissue in male Wistar rats exposed to a realistic dosage of Cr(VI) (20 mg/kg/b.w./day) through drinking water, based on the levels of these metals found in the environment, for a duration of 15, 30 and 60 days. The protective effect of melatonin (10 mg/kg) was also studied by simultaneous administration with the metal. Levels of enzymatic and non-enzymatic antioxidants as well as lipid peroxidation were assessed. There was a significant decrease in enzymatic as well as non-enzymatic antioxidants and an increase in the lipid peroxidation level, which were prevented and maintained at near-normal levels by the administration of melatonin in all treatment periods. Metal accumulation was maximal at 15 days, with gradual decreases till 60 days. Histopathological observations also demonstrated the fact that Cr (VI) exposure leads to cytological lesions in the hepatic tissue promoting cellular necrotic/apoptotic changes, while melatonin was able to counteract insults induced by Cr (VI) at all treatment periods. It also prevented alterations in insulin and glucose levels. Overall, the present study suggests a duration-dependent effect of Cr on hepatic oxidative stress and cytotoxicity and shows the potent activity of melatonin in preventing the negative effects of Cr (VI).

A combination of melatonin and alpha lipoic acid has greater cardioprotective effect than either of them singly against cadmium-induced oxidative damage.

Present study evaluates cardioprotective role of melatonin (Mel), alpha lipoic acid (ALA), a combination of melatonin and alpha lipoic acid (Mel + ALA) against cadmium (Cd)-induced oxidative damage. Female albino rats were subjected to 15-day exposure to Cd (5.12 mg/kg bw) alone or treated with ML (10 mg/kg bw) + ALA (25 mg/kg bw) simultaneously. Plasma markers of cardiac damage, cardiac free radical generation, lipid peroxidation, endogenous antioxidant status, cadmium load, metallothionein induction, and histopathology were evaluated in various experimental groups. Combination of Mel + ALA significantly prevented leakage of marker enzymes of cardiac damage, changes in cardiac free radical generation, endogenous antioxidants, antioxidant status, structural alterations and augmented the degree of metallothionein (MT) induction. The results demonstrate that ML + ALA co-administration effectively protected against Cd-induced cardiac oxidative damage.