Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice.

INTRODUCTION: Arsenic, an environmental contaminant naturally occurred in groundwater and has been found to be associated with immune-related health problems in humans. OBJECTIVE: In view of increasing risk of arsenic exposure due to occupational and non-occupational settings, the present study has been focused to investigate the protective efficacy of amla against arsenic-induced spleenomegaly in mice. RESULTS: Arsenic exposures (3 mg/kg body weight p.o for 30 days) in mice caused an increase production of ROS (76%), lipid peroxidation (84%) and decrease in the levels of superoxide dismutase (53%) and catalase (54%) in spleen as compared to controls. Arsenic exposure to mice also caused a significant increase in caspases-3 activity (2.8 fold) and decreases cell viability (44%), mitochondrial membrane potential (47%) linked with apoptosis assessed by the cell cycle analysis (subG1-28.72%) and annexin V/PI binding in spleen as compared to controls. Simultaneous treatment of arsenic and amla (500 mg/kg body weight p.o for 30 days) in mice decreased the levels of lipid peroxidation (33%), ROS production (24%), activity of caspase-3 (1.4 fold), apoptosis (subG1 12.72%) and increased cell viability (63%), levels superoxide dismutase (80%), catalase (77%) and mitochondrial membrane potential (66%) as compared to mice treated with arsenic alone. CONCLUSIONS: Results of the present study indicate that the effect of arsenic is mainly due to the depletion of glutathione in liver associated with enhanced oxidative stress that has been found to be protected following simultaneous treatment of arsenic and amla.

Factors Influencing Surgical Choices in Breast Cancer Treatment in India: A Comparative Study of Breast-Conserving Surgery vs Mastectomy.

Background Breast-conserving surgery (BCS) can make breast cancer treatment less disfiguring and more aesthetically acceptable for women. However, very few patients in India chose to undergo BCS surgery despite eligibility. Therefore, this study aims to explore the factors influencing the surgical choice in the treatment of breast cancer in India. Materials and methods This prospective study was conducted at a tertiary care hospital in Central India. Women having stage I/ II breast cancer diagnosis with a tumor size <5 cm were considered. A detailed self-designed questionnaire was used. A chi-square test with a significance level (p-value <0.05) was applied. Results Out of 40 females, 80% (n = 32) chose modified radical mastectomy (MRM), whereas 20% (n = 8) opted for BCS. The primary motivations to undergo MRM included concern about cancer recurrence (30%, n = 12), desire to avoid the adverse effects of radiation therapy (25%, n = 10), and fear of radiation therapy (20%, n = 8). Surgeons play a dominant role in determining surgical options, with 80% of MRM cases following the surgeon's recommendation. A significant association was observed between surgical options, education, economic status, locality, and family history (p<0.001). Changes in decision-making regarding the type of surgery after admission to the hospital were significant (p<0.001) after counseling. Conclusions The choice between breast conservation and mastectomy is influenced by sociodemographic factors, personal views, and surgeons' recommendations. Thus, these factors must be considered in preoperative counseling to help patients make informed choices.

Linear PEI nanoparticles: efficient pDNA/siRNA carriers in vitro and in vivo.

Linear polyethylenimine (lPEI, 25 kDa) nanoparticles' (LPN) series was synthesized by varying percentage of cross-linking with 1,4-butanediol diglycidyl ether (BDE) and their size, surface charge, morphology, pDNA protection/release, cytotoxicity and transfection efficiency were evaluated. Synthesized nanoparticles (NPs) were spherical in shape (size: ∼109 - 235 nm; zeta potential: +38 to +16 mV). These NPs showed increased buffering capacity with increasing percent cross-linking and also exhibited excellent transfection efficiency (i.e., ∼1.3 - 14.7 folds in case of LPN-5) in comparison with lPEI and the commercial transfection agents used in this study. LPN-5 based GFP-specific siRNA delivery resulted in ∼86% suppression of targeted gene expression. These particles were relatively nontoxic in vitro (in cell lines) and in vivo (in Drosophila). In vivo gene expression studies using LPN-5 in Balb/c mice through intravenous injection showed maximum expression of the reporter gene in the spleen. These results together demonstrate the potential of these particles as efficient transfection reagents. FROM THE CLINICAL EDITOR: The authors demonstrate a novel method of synthesizing linear PEI nanoparticles to utilize these as transfection agents.

Carcinoma Lung Presenting with Skeletal Muscle Metastasis: Case Report with Review of Literature.

Lung cancers usually present very late with distant metastasis, thereby carrying a poor prognosis. Metastasis at unusual sites such as extremity musculature does create a diagnostic challenge. This leads to delay in diagnosis and treatment initiation and further worsens the prognosis of the patient. Not many cases have been reported as of now and no standard guidelines are available regarding clinical approach in such cases. We have presented one of such cases to emphasize on importance of early detection and differentiation of such lesions from primary soft tissue malignancies.

Erratum to: Carcinoma Lung Presenting with Skeletal Muscle Metastasis: Case Report with Review of Literature.

[This corrects the article DOI: 10.1055/s-0041-1731636.].

Accelerated and scarless wound repair by a multicomponent hydrogel through simultaneous activation of multiple pathways.

Scarless healing of injury remains a clinical challenge because of its complicated and overlapping phases of inflammation, clearing, and regeneration. Curcumin has been already established as a potential wound healing agent for normal and diabetic-impaired wounds. Herein, the question has been addressed whether a well-known antioxidant cerium oxide nanoparticle (CNP) can potentiate the activity of curcumin to promote a cellular program for scarless healing. In this study, we have developed a biocompatible poly (acrylamide) hydrogel (PAGE)-based dressing material comprising of CNP and curcumin (ACC) and tested its wound healing activity in an animal model of acute wound. Characterization of the CNP- and curcumin-entrapped hydrogel dressing (ACC) demonstrated high loading efficiency and sustained release of curcumin. In a full-thickness acute wound healing model of rat, a single application of ACC dressing demonstrated higher wound healing efficacy (78%) and negligible scarring compared to dressings containing only curcumin or CNP in 7 days. Enhanced cell proliferation, higher collagen content, advanced wound maturity, re-epithelialization, and granulation tissue formation were observed using the combination of curcumin and CNP (ACC). Study of cellular mechanisms identified MCP-1 and TGF-ß as the key drivers of differential and accelerated healing observed in the ACC group. These, coupled with the upregulation of growth-related signaling pathways (HER2/ErbB2, TGF-ß-Smad2/3, MAPK/ERK, AKT, and VEGF), promoted almost scarless healing in animals treated with ACC. The optimized combination of curcumin and CNP used in our study shows distinct advantage and can be a better agent for complete wound healing.

A rare case of large jejunal diverticulum presenting as intestinal obstruction due to small bowel volvulus.

Jejunal diverticula are quite rare. Furthermore, small bowel diverticular disease resulting in volvulus can lead to complications necessitating surgical intervention. In this manuscript, we report a case of large sacculated jejunal diverticulum causing small bowel volvulus in a 40-year male. The jejunal mesentery at the base of the diverticulum was adhered to the terminal ileal mesentery forming a narrow base and complete small bowel going into volvulus by rotating around the narrow base. This case highlights a large jejunal diverticulum causing small bowel volvulus as an uncommon mechanism of complete small bowel volvulus. Although a rare entity, familiarity with jejunal diverticular disease, its complications and its management should be part of every surgeon's base of knowledge when considering abdominal pathology.

Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves.

Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

Potential risk of acute hepatotoxicity of kodo poisoning due to exposure to cyclopiazonic acid.

Kodo millet (Paspalum scrobiculatum L.) is a staple food of some sections of people of North India. Consumption of Kodo millet is often found to cause intoxication and poisoning. The grains are frequently infested with Aspergillus tamarii Kita, which produced substantial amount of a mycotoxin, cyclopiazonic acid (CPA). Investigations were carried out to evaluate the hepatotoxic/preneoplastic changes in rat liver following single and multiple dose administration of CPA. Results showed a marked increase in the activity of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) following CPA exposures, suggesting acute hepatotoxicity. Significant increase was also observed in gamma glutamyl transpeptidase (GGT) activity following CPA exposures, indicating preneoplastic changes in the liver. The results reveal that Kodo poisoning might cause acute hepatotoxicity in men and animals. The findings thus suggest that the consumption of contaminated Kodo millet is a serious health hazard due to exposure to CPA produced by Aspergillus tamarii associated with the millet.

Understanding the mechanism of atovaquone drug resistance in Plasmodium falciparum cytochrome b mutation Y268S using computational methods.

The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum). In this study, we examined the resistance mechanism against ATQ in P. falciparum through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP) of P. falciparum using composite modeling method by combining threading, ab initio modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.

Correlation of phthalate exposures with semen quality.

Phthalates are widely used man-made chemical released in the environment and human exposure is mainly through diet. As the phthalate plasticizers are not covalently bound to PVC, they can leach, migrate or evaporate into the environment and as a result have become ubiquitously contaminants. The present study investigates the correlation, if any, between the phthalate esters (DEP, DEHP, DBP, DMP, DOP) and sperm mitochondrial status, ROS, LPO, SCSA, and sperm quality. The study was conducted in the urban/rural population of Lucknow visiting Obstetrics and Gynecology Department, CSMMU, Lucknow. Semen analysis was performed according to the WHO guidelines while phthalate analysis by HPLC and LPO by spectrophotometer and the sperm mitochondrial status, ROS, SCSA using flow cytometry. The questionnaire data showed no significant difference in the demographic characteristics among the groups. In general, urban population was found to have statistically significant higher levels of phthalate esters than the rural. Further, infertile men showed statistically significant (p<0.05) higher levels of pollutants in the semen than fertile men. A negative correlation between semen phthalate level viz DEHP and sperm quality and positive association with depolarized mitochondria, elevation in ROS production and LPO, DNA fragmentation was established. The findings are suggestive that phthalates might be one among the contributing factors associated with the deterioration in semen quality and these adverse effects might be ROS, LPO and mitochondrial dysfunction mediated.