Synergistic effect of methanol extract of Abies webbiana leaves on sleeping time induced by standard sedatives in mice and anti-inflammatory activity of extracts in rats

During the determination of LD50 values of extracts of Abies webbiana, it was observed that the methanol extract (MEAW) produces sedation of animals. This led to investigation of the effect of MEAW on sleeping time in mice. When various doses of the methanol extract (100, 150, and 200 mg/kg body weight) were administered alone, no hypnotic activity was observed. However, these exhibited significant synergistic effects (P < 0.001) at those dose levels in mice when administered prior to the administration of standard sedatives (pentobarbitone sodium: 50 mg/kg and diazepam: 6 mg/kg, respectively). In addition anti-inflammatory effects of methanol, chloroform, and petroleum ether extracts of Abies webbiana leaves in rats were performed to assess scientific validity of the medicinal claim of Indian folk medicine. The effects of leaf extracts (methanol, chloroform, and petroleum ether) against inflammation were studied by carrageenan-induced paw edema model in rats. The methanol extract (400 mg/kg p.o.) of leaves of Abies webbiana showed the best significant anti-inflammatory activity as compared to that of diclofenac sodium (150 mg/kg p.o.). The LD50 values of methanol, chloroform, and petroleum ether extracts were found to be 986, 1387, and > 3200 mg/kg, respectively. Thus, the therapeutic index of methanol extract may be favorable to open a new vista on combination therapy of hypnotics and may also against inflammation.     

N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein,microtubule organization,and telomeric DNA

Background  

Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is able to induce senescence in the HCT-116 colon cancer cell line.     

Long-term suppression of weight gain,adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes

Intracerebroventricular administration of recombinant adeno-associated virus (rAAV) encoding the rat leptin gene (rAAV-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and FFA. Serum ghrelin levels were increased in young but not older rats. Central rAAV-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown by expression of uncoupling protein mRNA in brown adipose tissue. The sustained decrease in appetite seemingly resulted from attenuation of appetite-stimulating neuropeptide Y and enhancement of appetite-inhibiting melanocortin signalings in the hypothalamus. Neither the onset of pubertal sexual maturation nor reproductive cyclicity in adult female rats was affected by the sustained reduction in energy consumption and weight gain. These findings demonstrate that central leptin gene therapy in prepubertal rats is a novel therapy to control postpubertal weight gain, adiposity, and hyperinsulinemia for extended periods.     

Effect of lead exposure on the immune response of some occupationally exposed individuals

Lead is a ubiquitous pollutant in the industrial environment, which poses serious threats to human health. In the past 20 years increasing attention has been paid to the effects of lead exposure on health. This toxic metal alters the immune response of animals as well as humans. To study the immunological effects of occupational exposure to lead, we examined lymphocyte proliferation, natural killer (NK) cell cytotoxicity and interferon-gamma production with peripheral blood mononuclear cells (PBMCs) of individuals occupationally exposed to lead. We selected three different groups of individuals exposed to lead: three-wheeler drivers (30), battery workers (34) and silver jewelery makers (20); and unexposed healthy volunteers (30) as control for comparison. Our results indicate that though lymphocyte proliferation to phytohaemagglutinin (PHA) is inhibited in lead exposed individuals as compared with unexposed volunteers, there is no correlation between inhibition of lymphocyte proliferation and blood lead level. NK cell cytotoxicity remains unaffected in individuals exposed to lead as compared with controls. On the other hand, we observed that interferon-gamma (IFN-gamma) was significantly elevated in T cell mitogen, PHA, stimulated PBMCs culture supernatant of lead exposed individuals. We found significant positive correlation between blood lead levels and IFN-gamma produced in culture supernatant on stimulation with PHA. In brief, this study demonstrates that lead can affect the immune response of the occupationally exposed individuals such as three-wheeler drivers, battery reconditioning workers and silver jewelery makers.     

Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin

OBJECTIVE: In order to circumvent the multiple peripheral effects of hyperleptinemia and leptin resistance, the efficacy of leptin transgene expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the central energy homeostasis in obesity was examined. RESEARCH METHODS AND PROCEDURES: A recombinant adeno-associated viral vector encoding either leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP) was microinjected into the PVN of obesity-prone rats consuming a high-fat diet (HFD). RESULTS: rAAV-lep, and not rAAV-GFP, microinjection significantly reduced energy intake and enhanced energy expenditure, thereby resulting in normalization of weight and blood levels of leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin secretion during the extended period of observation. DISCUSSION: Thus, we show, for the first time, that amelioration of leptin insufficiency with enhanced localized leptin availability in the PVN alone can reverse dietary obesity and the attendant hyperinsulinemia and concurrently block the central stimulatory effects of elevated endogenous ghrelin on food intake and adiposity.     

SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions

Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on proliferation, morphology, and cell density of glioma cells grown in vitro, in the absence and presence of ECM proteins under standard (10% fetal bovine serum [FBSI) and reduced (0.1% FBS) serum stress conditions. Under standard conditions, MTT (3-(4,5-cimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) growth curves, morphology, and Western blot analyses demonstrated that SPARC had a suppressive and biphasic effect on growth that was not grossly modulated by the ECMs. The SPARC-induced changes in morphology observed at 24 h were not altered by the presence of ECMs. Under reduced-serum stress conditions, Western blot, morphological, and flow cytometric analyses indicated that the SPARC-induced suppressive growth effects were eliminated when the cells were grown on plastic. However, ECM-specific changes in growth were observed, some of which correlated with secreted SPARC levels. These results indicate that the differential effects of SPARC and ECMs on proliferation are dependent on culture conditions. Since the results obtained under standard conditions agree with our in vivo observations, we conclude that the ability of SPARC to suppress proliferation is regulated to a greater degree by the level of SPARC and that this suppressive effect is not influenced by the presence of any of the ECMs examined.     

Expression of extracellular matrix metalloprotease inducer in laryngeal squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Head and neck cancer tumor cell invasion is responsible for both local destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesize that EMMPRIN is overexpressed in laryngeal cancer. STUDY DESIGN: Retrospective analysis of patients with supraglottic laryngeal cancer. METHODS: Total protein immunoblotting and immunohistochemical analysis of normal and malignant tissue were performed to determine EMMPRIN expression. EMMPRIN immunoreactivity in 33 patients was correlated with clinicopathological features and survival. RESULTS: Whole-tissue lysates of tumors (n = 8) and metastatic lymph nodes (n = 2), but not normal skin (n = 8) or mucosa (n = 6), expressed significant amounts of EMMPRIN by immunoblotting. EMMPRIN membrane immunoreactivity (transmembrane EMMPRIN score) was associated with nodal positivity (P =.07), and it was a borderline significant predictor of survival (Hazards Ratio = 2.4; 95% CI, 0.88-6.55). As a categorical variable, higher transmembrane EMMPRIN score was associated with higher mortality. CONCLUSIONS: The present study helps to establish EMMPRIN as a widely expressed protein in dysplastic mucosa and supraglottic laryngeal cancer, but not in normal epithelial counterparts.     

Radiological review of rhinocerebral mucormycosis cases during the COVID-19 Pandemic: A single-center experience

Mucormycosis is caused by the fungi belonging to the order Mucorales and class Zygomycetes. The incidence of mucormycosis has increased with the onset of the severe acute respiratory syndrome coronavirus 2 infections leading to the coronavirus disease 2019 (COVID-19) pandemic. This rise is attributed to the use of immunosuppressive medication to treat COVID-19 infections. Authors have retrospectively collected data of our cases of mucormycosis diagnosed from April 2020 to April 2021 at our institute. A total of 20 patients with rhinocerebral mucormycosis were studied. Most of the study subjects were male patients (90%) and were of the age group 41-50 years. Most patients in the review had comorbidities (85%) with diabetes being the most common comorbidity. Para nasal sinuses were involved in all the cases. Involvement of the neck spaces was present in 60% of the cases. Involvement of the central nervous system was present in 80% of the cases. Orbital involvement was present in 90% of the cases. The authors reviewed the various imaging findings of mucormycosis on computed tomography and magnetic resonance imaging in this article.