New challenges in the use of nanomedicine in cancer therapy.

Nanomedicines are applied as alternative treatments for anticancer agents. For the treatment of cancer, due to the small size in nanometers (nm), specific site targeting can be achieved with the use of nanomedicines, increasing their bioavailability and conferring fewer toxic side effects. Additionally, the use of minute amounts of drugs can lead to cost savings. In addition, nanotechnology is effectively applied in the preparation of such drugs as they are in nm sizes, considered one of the earliest cutoff values for the production of products utilized in nanotechnology. Early concepts described gold nanoshells as one of the successful therapies for cancer and associated diseases where the benefits of nanomedicine include effective active or passive targeting. Common medicines are degraded at a higher rate, whereas the degradation of macromolecules is time-consuming. All of the discussed properties are responsible for executing the physiological behaviors occurring at the following scale, depending on the geometry. Finally, large nanomaterials based on organic, lipid, inorganic, protein, and synthetic polymers have also been utilized to develop novel cancer cures.

Environmental and occupational determinants of myelodysplastic syndrome: A case-control study from Pakistan.

BACKGROUND: Myelodysplastic syndromes (MDS) are heterogeneous group of haematopoietic stem cell disorders and have variable reduction in the production of red cells, platelets and mature granulocytes. AIM: We conducted a case-control study evaluating the environmental and occupational determinants as risk factors of MDS. METHODS: A case-control study was conducted including 150 de novo MDS cases and 450 age and gender-matched controls. Disease characteristics, sociodemographics and exposure to environmental and occupational determinants were collected through a questionnaire. Chi-square test was applied to observe association, and binary logistic regression was applied to predict the odds of having MDS. RESULTS: A total of 600 participants were analysed. Those who were exposed to arsenic (OR 31.81, CI: 19.0-53.0, P-value: .000), benzene (OR 1.564, CI: 1.07-2.27, P-value: .01) using natural source of water (OR 3.563, CI: 2.29-5.53, P-value: .000) and smokers (OR 3.1, P-value: .000) were more likely to have MDS. Unmarried were less likely to acquire MDS than married (OR 0.239, CI: 0.15-0.36, P-value: .000), Sindhi speaking were 1.419 times more likely to have MDS than participants speaking other languages. Uneducated participants were more likely to have MDS than educated and powder milk users were more likely to have MDS than dairy milk users. CONCLUSION: Our results revealed that arsenic, use of natural source of water and benzene exposure might lead to higher risk of acquiring MDS. This study would be helpful to understand the aetiology of disease in Pakistani population.

Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics.

Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics. Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters. Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 µmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 µmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 µmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients' group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls. Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.

Environmental determinants of aplastic anemia in Pakistan: a case-control study.

AIM: Aplastic anemia (AA) affects the Asian population two to three fold more than people in other regions. Besides the host genetics and socioeconomic status, several other environmental exposures have been linked with an AA etiology. We aimed to examine the association of various environmental exposures with AA occurrence among Pakistani individuals. SUBJECTS AND METHODS: A case-control study was conducted in Karachi, Pakistan, where cases (diagnosed AA patients) were selected from the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD), while for each case, a single control (who was free of AA and visited the outpatient department of the same hospital for the treatment of minor ailments) was selected matched by age and sex. A total of 428 participants were included in this study with equal proportions of cases and controls. Information related to disease characteristics, sociodemographics and exposure to chemicals was collected through a survey questionnaire, laboratory investigations and medical records. Descriptive results were reported as frequencies and proportions, adjusted odds ratios with 95 % confidence intervals and population attributable risk (PAR) as percentage. RESULTS: Among study participants (n = 428), AA was significantly associated with various environmental exposures. Participants residing in rural settings (OR = 2.29, 95 % CI 1.12-4.67, p-value < 0.01) and those who reported exposure to pesticides (OR = 3.58, 95 % CI 1.27-10.10, p-value 0.01; PAR = 18.16 %) were significantly more likely to report AA. Participants with a formal education were significantly less likely to have AA (OR = 0.27, 95 % CI 0.10-0.71, p-value < 0.01). CONCLUSIONS: This study observed a significant association of aplastic anemia with a lower socioeconomic profile, and certain environmental exposures among the Pakistani population. The evidence may be helpful in understanding the pathophysiology of aplastic anemia in the context of environmental exposures.

BAD, a Proapoptotic Protein, Escapes ERK/RSK Phosphorylation in Deguelin and siRNA-Treated HeLa Cells.

This study has been undertaken to explore the therapeutic effects of deguelin and specific siRNAs in HeLa cells. The data provided clearly show the silencing of ERK 1/2 with siRNAs and inhibition of ERK1/2 with deguelin treatment in HeLa cells. Additionally, we are providing information that deguelin binds directly to anti-apoptotic Bcl-2, Bcl-xl and Mcl-1 in the hydrophobic grooves, thereby releasing BAD and BAX from dimerization with these proteins. This results in increased apoptotic activity through the intrinsic pathway involved in rupture of mitochondrial membrane and release of cytochrome C. Evidence for inhibition of ERK1/2 by deguelin and escape of BAD phosphorylation at serine 112 through ERK/RSK pathway has been further fortified by obtaining similar results by silencing ERK 1/2 each with specific siRNAs. Increase in BAD after treatment with deguelin or siRNAs has been interpreted to mean that deguelin acts through several alternative pathways and therefore can be used as effective therapeutic agent.

Current view from Alzheimer disease to type 2 diabetes mellitus.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to memory problems. It has been associated with type 2 diabetes mellitus at both the molecular and biochemical level. Pancreatic cells have molecular similarities to the brain at the transcriptomic and proteomic levels. Several genes have been reported to be responsible for both AD and diabetes. Currently, no proper treatment is available but various therapeutic approaches are utilized worldwide for the management of these disorders and may be nanoparticles and herbal treatment of Bacopa monnieri will make promise for the treatment of AD in future. The formation of amyloids in neurons and the formation of amylin in pancreatic cells are potential links between these two disorders, which can be silent killers.