Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells

Photodynamic therapy (PDT) is a clinical approach that utilizes light-activated drugs for the treatment of a variety of pathologic conditions. Human poorly (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells undergo rapid apoptosis when treated with PDT sensitized with Hypocrellin A (HA) and Hypocrellin B (HB). It has been shown that these compounds have a strong photodynamic effect on tumors and viruses. The initiating events of PDT sensitized HA and HB-induced apoptosis are poorly defined. In the current study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HA and HB-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases-8 and -3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photoactivation of HA and HB enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/ CD95L expression appeared within 2 h following light activation and appeared to be a primary event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm is a secondary event following the activation of initiator caspase-8 preceding caspase-3 activation, cleavage of PARP and DNA fragmentation. Cytochrome c appeared in the cytosol within 2-3 h post PDT. Cleavage of PARP was observed at 3-4 h following PDT and caspase-3 specific inhibitor DEVD-CHO and broad-spectrum caspases inhibitor z-VAD-fmk blocked caspase-3 activation and PARP cleavage suggesting that caspase-3 plays an important role in HA and HB-induced apoptosis.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Dietary patterns and health-related quality of life among Iranian adolescents

Quality of Life Research - Examining the associations of a-posteriori-defined dietary patterns and health-related quality of life (HRQOL) among Iranian adolescents. This cross-sectional study was...     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry

BackgroundObesity has been described as a protective factor in cardiovascular and other diseases being expressed as ‘obesity paradox’. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI).MethodsWe retrospectively collected data up to May 31^st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m²; n = 1110, 25?30 kg/m²; n = 1464, and >30 kg/m²; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed.ResultsThe rate of respiratory insufficiency was more recorded in BMI 25?30 kg/m² as compared to BMI < 25 kg/m² (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m² than BMI < 25 kg/m², respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m² and BMI > 30 kg/m² did not impact the mortality rate (HR 1.15, 95% CI: 0.889?1.508; p = 0.27) (HR 1.15, 95% CI: 0.893?1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m² is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538?1.004; p = 0.05).ConclusionsHOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.     

Healthcare Cost Savings Associated with Increased Whole Grain Consumption among Australian Adults

Many dietary guidelines emphasise “mostly” whole grain food choices as part of an overall healthy eating pattern based on evidence for enhancing nutritional status and reducing chronic disease. Still, countries including Australia fall short of their consumption targets. Furthermore, healthcare cost savings associated with increasing the consumption of whole grains in alignment with the Daily Target Intake (DTI) recommendation of 48 g are unknown. The aim of this study was to assess the potential savings in costs of healthcare and lost productivity associated with a reduction in the incidence of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease (CVD) through meeting the 48 g DTI recommendation for whole grains among the Australian adult population (>20 years). A three-step cost-of-illness analysis was conducted using input parameters from: 1) estimates of proportions of consumers (5%, 15%, 50%, and 100%) who would increase their current intake of whole grains to meet the recommended DTI in Australia; 2) relative reductions in risk of T2DM and CVD associated with specific whole grain consumption, as reported in meta-analysis studies; and 3) data on costs of healthcare and productivity loss based on monetary figures by national healthcare authorities. A very pessimistic (5% of the population) through to universal (100% of the population) adoption of the recommended DTI was shown to potentially yield AUD 37.5 (95% CI 22.3–49.3) to AUD 750.7 (95% CI 445.7–985.2) million, and AUD 35.9 (95% CI 8.3–60.7) to AUD 717.4 (95% CI 165.5–1214.1) million in savings on annual healthcare and lost productivity costs for T2DM and CVD, respectively. Given such economic benefits of the recommended consumption of whole grains, in exchange for refined grains, there is a real opportunity to facilitate relevant socioeconomic cost-savings for Australia and reductions in disease. These results are suggestive of a much greater opportunity to communicate the need for dietary change at all levels, but particularly through food-based dietary guidelines and front-of-pack labelling initiatives.     

Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice

Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p < 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p < 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p < 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.