Enhancement of Vitamin C's Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study.

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of -4.9 kcal/mol compared to -4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5-3.5 Å. H-bonds provide directed, high-affinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone).

The current study was conducted to determine the precise mechanisms of Sirtuin-1 (Sirt-1), TGF- ß (Transforming Growth Factor-ß), and long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT-1) in signaling pathways in doxorubicin (DOX)-induced nephrotoxicity. The potential therapeutic effect of Resveratrol and Pirfenidone in DOX toxicity was also assessed. Thirty-six male adult rats were evenly distributed into four groups: Group 1: control rats. Group 2: DOX exposed rats' group, each animal received 7.5 mg/kg DOX as a single intravenous dose, Group 3: DOX exposed group subjected to oral resveratrol (20 mg/kg/daily for two weeks), Group 4: DOX exposed group subjected to oral Pirfenidone (200 mg/kg once daily for 10 days). At the planned time, animals were sacrificed. Renal tissue was collected to assess matrix metalloproteinase-9 (MMP9), inflammatory and apoptotic markers: tumor necrosis factor-alpha (TNF- ß, caspase-3, cyclo-oxygenase-2 (COX-2), and oxidative stress markers: nitric oxide (NO), Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). Sirtuin-1 (Sirt-1), TGF-ß, and LncRNA MALAT-1 were quantitatively assessed by real-time RT-PCR in the whole blood. Results showed that the DOX group exhibited a significant increase in oxidative stress markers, and inflammatory, and apoptotic markers in the renal tissue. Histologically, the renal tubule lining cells exhibited vacuolar alterations in the cytoplasm, glomerular atrophy, and vascular congestion. Furthermore, renal degeneration was evident, as confirmed by the heightened immuno-expression of MMP9. Exposure to DOX resulted in a significant decrease in Sirtuin-1 (Sirt-1) with a significant increase in the TGFß, and LncRNA MALAT-1 gene expression. However, pre-treatment with either resveratrol/or Pirefenidone ameliorated the histological renal alterations, regulated the pathways of Sirt-1, TGFß, and LncRNA MALAT-1, and decreased all oxidative stress, inflammatory and apoptotic markers. In conclusion, DOX exposure leads to renal toxicity by inducing renal degeneration, oxidative stress, and apoptosis. Administration of either resveratrol or Pirfenidone counteracted these changes and protected the kidney against DOX-induced renal damage.

Impact of vitamin D in children with chronic tonsillitis (immunohistochemical study of CD68 polarisation and proinflammatory cytokines estimation).

Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children's patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case-control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3-6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group (P < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group (P < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant (P = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group (P < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children.

Ultrastructural analysis of zinc oxide nanospheres enhances anti-tumor efficacy against Hepatoma.

Zinc oxide nanomaterial is a potential material in the field of cancer therapy. In this study, zinc oxide nanospheres (ZnO-NS) were synthesized by Sol-gel method using yeast extract as a non-toxic bio-template and investigated their physicochemical properties through various techniques such as FTIR, XR, DLS, and TEM. Furthermore, free zinc ions released from the zinc oxide nanosphere suspended medium were evaluated by using the ICP-AS technique. Therefore, the cytotoxicity of ZnO nanospheres and released Zn ions on both HuH7 and Vero cells was studied using the MTT assay. The data demonstrated that the effectiveness of ZnO nanospheres on HuH7 was better than free Zn ions. Similarly, ZnO-Ns were significantly more toxic to HuH7 cell lines than Vero cells in a concentration-dependent manner. The cell cycle of ZnO-Ns against Huh7 and Vero cell lines was arrested at G2/M. Also, the apoptosis assay using Annexin-V/PI showed that apoptosis of HuH7 and Vero cell lines by ZnO nanospheres was concentration and time-dependent. Caspase 3 assay results showed that the apoptosis mechanism may be intrinsic and extrinsic pathways. The mechanism of apoptosis was determined by applying the RT-PCR technique. The results revealed significantly up-regulated Bax, P53, and Cytochrome C, while the Bcl2 results displayed significant down-regulation and the western blot data confirmed the RT-PCR data. There is oxidative stress of the ZnO nanospheres and free Zn+2 ions. Results indicated that the ZnO nanospheres and free Zn+2 ions induced oxidative stress through increasing reactive oxygen species (ROS) and lipid peroxidation. The morphology of the HuH7 cell line after exposure to ZnO nanospheres at different time intervals revealed the presence of the chromatin condensation of the nuclear periphery fragmentation. Interestingly, the appearance of canonical ultrastructure features of apoptotic morphology of Huh7, Furthermore, many vacuoles existed in the cytoplasm, the majority of which were lipid droplets, which were like foamy cells. Also, there are vesicles intact with membranes that are recognized as swollen mitochondria.

Evaluating Pain Management Practices for Cancer Patients among Health Professionals: A Global Survey.

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients' reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large.

Global Survey of the Roles, Satisfaction, and Barriers of Home Health Care Nurses on the Provision of Palliative Care.

Background: The World Health Assembly urges members to build palliative care (PC) capacity as an ethical imperative. Nurses provide PC services in a variety of settings, including the home and may be the only health care professional able to access some disparate populations. Identifying current nursing services, resources, and satisfaction and barriers to nursing practice are essential to build global PC capacity. Objective: To globally examine home health care nurses' practice, satisfaction, and barriers, regarding existing palliative home care provision. Design: Needs assessment survey. Setting/Subjects: Five hundred thirty-two home health care nurses in 29 countries. Measurements: A needs assessment, developed through literature review and cognitive interviewing. Results: Nurses from developing countries performed more duties compared with those from high-income countries, suggesting a lack of resources in developing countries. Significant barriers to providing home care exist: personnel shortages, lack of funding and policies, poor access to end-of-life or hospice services, and decreased community awareness of services provided. Respondents identified lack of time, funding, and coverages as primary educational barriers. In-person local meetings and online courses were suggested as strategies to promote learning. Conclusions: It is imperative that home health care nurses have adequate resources to build PC capacity globally, which is so desperately needed. Nurses must be up to date on current evidence and practice within an evidence-based PC framework. Health care policy to increase necessary resources and the development of a multifaceted intervention to facilitate education about PC is indicated to build global capacity.

Refugees in Conflict: Creating a Bridge Between Traditional and Conventional Health Belief Models.

The recent wave of migration from Middle Eastern countries to Europe presents significant challenges to the European health profession. These include the inevitable communication gap created by differences in health care beliefs between European oncologists, health care practitioners, and refugee patients. This article presents the conclusions of a workshop attended by a group of clinicians and researchers affiliated with the Middle East Cancer Consortium, as well as four European-based health-related organizations. Workshop participants included leading clinicians and medical educators from the field of integrative medicine and supportive cancer care from Italy, Germany, Turkey, Israel, Palestine, Iran, Lebanon, Jordan, Egypt, and Sudan. The workshop illustrated the need for creating a dialogue between European health care professionals and the refugee population in order to overcome the communication barriers to create healing process. The affinity for complementary and traditional medicine (CTM) among many refugee populations was also addressed, directing participants to the mediating role that integrative medicine serves between CTM and conventional medicine health belief models. This is especially relevant to the use of herbal medicine among oncology patients, for whom an open and nonjudgmental (yet evidence-based) dialogue is of utmost importance. The workshop concluded with a recommendation for the creation of a comprehensive health care model, to include bio-psycho-social and cultural-spiritual elements, addressing both acute and chronic medical conditions. These models need to be codesigned by European and Middle Eastern clinicians and researchers, internalizing a culturally sensitive approach and ethical commitment to the refugee population, as well as indigenous groups originating from Middle Eastern and north African countries. IMPLICATIONS FOR PRACTICE: European oncologists face a communication gap with refugee patients who have recently immigrated from Middle Eastern and northern African countries, with their different health belief models and affinity for traditional and herbal medicine. A culturally sensitive approach to care will foster doctor-refugee communication, through the integration of evidence-based medicine within a nonjudgmental, bio-psycho-social-cultural-spiritual agenda, addressing patients' expectation within a supportive and palliative care context. Integrative physicians, who are conventional doctors trained in traditional/complementary medicine, can mediate between conventional and traditional/herbal paradigms of care, facilitating doctor-patient communication through education and by providing clinical consultations within conventional oncology centers.