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.     

Modulation of mouse skin tumor promotion by dietary 13-cis-retinoic acid and {alpha}-difluoromethylornithine

The effects of dietary supplementation of 13-cis-retinoic acid(13-cis-RA) and -difluoromethylornithine (DFMO) in the drinkingwater on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotedskin tumor formation was determined. Administration of 13-cis-RAin the diet and DFMO in the drinking water was started 1 weekand 2 days before the first TPA application to the dimethylbenz[a]anthracene-initiatedskin of either female CD-I or SENCAR mice, respectively. Dietary13-cis-RA failed to inhibit both the tumor yield and the incidence;papillomas per mouse at 0, 5, 50, 100 and 200 mg/kg diet 13-cis-RAdoses were 25, 30, 22, 28 and 25 respectively at 18 weeks ofpromotion treatment and at all doses 100% of the mice bore papillomas.However, dietary 13-cis-RA dramatically reduced the size ofskin tumor promoted with TPA. 13-cis-RA at doses of 5, 50, 100and 200 mg/kg diet inhibited skin papillomas (> 4 mm diameter)per mouse by 28, 55, 76 and 93%, respectively. Retinoid treatmentdid not affect body weight gains and the survival was more than80% in all groups. In accord with our previous findings, DFMOwhen given in drinking water, was a very effective inhibitorof mouse skin tumor promotion by TPA; DFMO at 0.25% concentrationinhibited the number of papillomas by 50%. Inhibition of skintumor promotion by combined treatments with dietary 13-cis-RA(100 mg/kg) and DFMO (0.25%) in the drinking water was possiblyadditive. The retinoid and DFMO preclude TPA-increased ornithinedecarboxylase (ODC) activity and the accumulation of putrescineby differential effects on ODC, an enzyme associated with skintumor promotion by TPA.     

A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases

Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.     

Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.     

Pakistan’s Response to COVID-19: Overcoming National and International Hypes to Fight the Pandemic

The COVID-19 outbreak started as pneumonia in December 2019 in Wuhan, China. The subsequent pandemic was declared as the sixth public health emergency of international concern on January 30, 2020, by the World Health Organization. Pakistan could be a potential hotspot for COVID-19 owing to its high population of 204.65 million and its struggling health care and economic systems. Pakistan was able to tackle the challenge with relatively mild repercussions. The present analysis has been conducted to highlight the situation of the disease in Pakistan in 2020 and the measures taken by various stakeholders coupled with support from the community to abate the risk of catastrophic spread of the virus.     

An Overview of the Treatment Options Used for the Management of COVID-19 in Pakistan: Retrospective Observational Study

BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.     

Impact of Mental Health Treatment on Suicide Attempts

This paper analyzes the impact of mental health treatment on suicide attempts. While prior work demonstrates the effectiveness of mental health treatment at reducing suicide risk, few studies examine nationally representative populations or use broad measures of access to mental health services. A methodological problem can arise in studies of mental health treatment and suicidal behavior because a suicide attempt can result in the use of more mental health services. Using nationally representative survey data combined with national estimates of provider availability, this paper employs a methodological correction to address that potential problem of reverse causation. This paper uses measures of the density of health care providers in an area as statistical instruments for use of mental health treatment in an analysis of the impact of mental health treatment on suicide attempts. This study finds that mental health treatment significantly reduces suicide attempts.

     

Undiagnosed Depression among Hypertensive Individuals in Gaza: A Cross-sectional Survey from Palestine

BackgroundThe aim of this study was to estimate the prevalence and to determine the associated factors of undiagnosed depression amongst hypertensive patients (HTNP) at primary health care centers (PHCC) in Gaza.MethodsA cross-sectional survey was conducted including 538 HTNP as a recruitment phase of a clustered randomized controlled trial. Data were collected through face-to-face structured interview, and depression status was assessed by Beck''s Depression Inventory (BDI-II). Data were analyzed by STATA version 14 using standard complex survey analyses, accounted for unresponsiveness and clustering approach. Generalized linear regression analysis was performed to assess associations.ResultsThe prevalence of undiagnosed clinical depression was 11.6% (95% confidence interval [CI]: 8.1, 16.3). Moreover, prevalence of 15.4% (95% CI: 10.8, 21.6) was found for mild depression symptoms. We found that non-adherence to antihypertensive medications (AHTNM) (β = 0.9, 95% CI: 0.17, 1.7), having more health-care system support (β = 2.8, 95% CI: 1.6, 3.9) and number of AHTNM (β = 1.5, 95% CI: 0.6, 2.5) remain significantly positively associated with BDI-II score. On the other hand, older age (β = -0.1, 95% CI: -0.2, -0.02), having better social support (β = -6.8, 95% CI: -8.9, -4.7) and having stronger patient-doctor relationship (β = -4.1, 95% CI: -6.9, -1.2) kept significantly negative association.ConclusionThe prevalence of undiagnosed depression was about one-quarter of all cases; half of them were moderate to severe. Routine screening of depression status should be a part of the care of HTNP in PHCC.     

Medical Marijuana Laws,Marijuana Use,and Opioid-Related Outcomes among Women in the United States

BackgroundIn the context of the opioid epidemic, a limited but growing body of literature has found state medical marijuana laws (MMLs) to be associated with lower levels of opioid prescribing. However, robust evidence linking state MMLs with individual-level opioid-related outcomes is lacking, particularly among women. This finding is especially true for pregnant and parenting women, who have been disproportionately affected by the opioid crisis.MethodsUsing data drawn from the 2002–2014 National Survey on Drug Use and Heath, the study uses a difference-in-differences estimation strategy to compare opioid-related outcomes (opioid misuse initiation, opioid misuse in the past month and past year, and opioid use disorder) among all women, pregnant women, and parenting women in states with and without MMLs (before and after implementation). The study also investigates the impact of MMLs on marijuana use and marijuana use disorder.ResultsThe findings indicate that MMLs were not associated with opioid misuse, opioid misuse initiation, or opioid use disorder among all women, pregnant women, and parenting women. These laws were, however, positively correlated with marijuana use and marijuana use disorder among all women and women with children. In addition, MMLs were associated with an increase in the frequency of opioid misuse for pregnant women and a decrease in the frequency of opioid misuse for parenting women.ConclusionsThis finding suggests that, although medical marijuana may be viewed by some as a substitute for opioid analgesics, MMLs may not be an effective policy tool to tackle the opioid epidemic among women, especially pregnant and parenting women.