Current status of beta-thalassemia and its treatment strategies.

BACKGROUND: Thalassemia is an inherited hematological disorder categorized by a decrease or absence of one or more of the globin chains synthesis. Beta-thalassemia is caused by one or more mutations in the beta-globin gene. The absence or reduced amount of beta-globin chains causes ineffective erythropoiesis which leads to anemia. METHODS: Beta-thalassemia has been further divided into three main forms: thalassemia major, intermedia, and minor/silent carrier. A more severe form among these is thalassemia major in which individuals depend upon blood transfusion for survival. The high level of iron deposition occurs due to regular blood transfusion therapy. RESULTS: Overloaded iron raises the synthesis of reactive oxygen species (ROS) that are noxious and prompting the injury to the hepatic, endocrine, and vascular system. Thalassemia can be analyzed and diagnosed via prenatal testing (genetic testing of amniotic fluid), blood smear, complete blood count, and DNA analysis (genetic testing). Treatment of thalassemia intermediate is symptomatic; however; it can also be accomplished by folic supplementation and splenectomy. CONCLUSION: Thalassemia major can be cured through regular transfusion of blood, transplantation of bone marrow, iron chelation management, hematopoietic stem cell transplantation, stimulation of fetal hemoglobin production, and gene therapy.

Cardiac toxicity of heavy metals (cadmium and mercury) and pharmacological intervention by vitamin C in rabbits.

Mercury and cadmium are highly dangerous metals that can lead to disastrous effects in animals and humans. The aim of the current research was to elucidate the poisonous effects of mercuric chloride and cadmium chloride individually and in combination on biochemical profiles of plasma and their accumulation in heart. The therapeutic effect of vitamin C against these metals in rabbits was also studied. Mercuric chloride (1.2 µg/g), cadmium chloride (1.5 µg/g), and vitamin C (150 µg/g of body weight) were orally given to treatment groups of the rabbits (1-control; 2-vitamin; 3-CdCl2; 4-HgCl2; 5-vitamin + CdCl2; 6-vitamin + HgCl2; 7-CdCl2 + HgCl2, and 8-vitamin + CdCl2 + HgCl2. After the biometric determination of all intoxicated rabbits, biochemical parameters, viz low-density lipoproteins (LDL), high-density lipoproteins (HDL), cholesterol, creatine kinase, and troponin T (TnT) were analyzed using available kits. Levels of cholesterol (0.7 ± 0.1 mmol/l), creatine kinase (2985.2 ± 11 IU/L), LDL (20.35 ± 1.31 mg/dl), and troponin T (1.22 ± 0.03 µg/l) were significantly (P < 0.05) increased. HDL (84.78 ± 4.30 mg/dl) was significantly (P < 0.05) decreased, while supplementation of vitamin C decreased the adverse effects of CdCl2 and HgCl2 on biochemical parameters in all metal-exposed groups. A similar trend was also seen in rabbits treated with CdCl2 + vitamin and vitamin + CdCl2 + HgCl2. Accumulation of Cd and Hg was higher in heart tissues. This study, therefore, provides awareness on the cardiac toxicity of mercury and cadmium chlorides in the rabbits and the possible protective role of vitamin C against the perturbations induced by metals.

Dose and duration-dependent toxicological evaluation of lead acetate in chicks.

Lead is one of the utmost contaminated and dangerous heavy metals. This toxicant ultimately enters into the human body through the food chain and accumulated in the body because the animal/human body has not an appropriate mechanism to excrete it from the body. The main objective of the present research was to assess the toxicological effects of lead on body weights, biochemical, and hematological parameters of chickens and also to measure its bioaccumulation in the brain. Lead acetate was administrated orally at doses of 0, 71, 142, 213, and 284 mg/kg of body weight of chicken for groups A, B, C, D, and E, respectively. Along with determination of biometry of all experimental chicks, hematological [hemoglobin (Hb), packed cell volume (PCV), mean corpuscular hemoglobin concentration (MCHC), total erythrocyte count (TEC), white blood cells (WBCs), leukocyte differential count (LDC)] and biochemical [low density lipoprotein (LDL), total protein, high-density lipoprotein (HDL), and alanine aminotransferase (ALT)] parameters were measured. The present study showed that the bodyweight of chickens was not affected significantly by lead acetate exposure. The levels of MCHC, PCV, TEC, Hb, LDL, HDL, and total protein were found to be significantly decreased while WBC, LDC, and ALT profile were enhanced due to administration of lead acetate. Bioaccumulation of lead acetate was found to be higher in the brain. We conclude that the chronic administration of lead acetate affected the blood and biochemical profile of exposed chicken. These effects might be due to the accumulation of the chemical in certain vital organ(s). However, further studies in the future are suggested to refine such findings.

Prevalence of Human Papilloma Virus Sub Genotypes following Head and Neck Squamous Cell Carcinomas in Asian Continent, A Systematic Review Article.

OBJECTIVES: In current era of blue brain intelligence and technology access at ease, standardization of disease etiology demands extensive research to drop-down human papilloma virus associated head and neck squamous cell carcinomas impact at large. Present retrospection aims to estimate comparative association of human papilloma virus sub-genotypes in head and neck squamous cell carcinomas, critical analysis of existing research gap, treatment progress, co-infection, gender association, national status and challenges following Human papilloma virus led head and neck squamous cell carcinomas among world largest continent. BACKGROUND: Head and neck squamous cell carcinomas are not just like malignancies of uterine cervix, lymph nodes and breast cancers. Human papilloma virus led head and neck squamous cell carcinomas treatment directly impact Central nervous system in humans. Intriguingly, human papilloma virus mediated immune response increases patient survival, which indirectly transmit human papilloma virus in future generations and act as a potential threat developing neurogenic disorders. METHODS: An objective based search strategy, following comprehensive and specific search approaches were made to retrieve recent 12 years research data from five different NCBI databases. Out of 300 shortlisted articles, only 24 principal studies met the inclusion criteria. RESULTS: Highest human papilloma virus prevalence (10.42 %) was found in South Asia, 5.8 % in South East Asia, 5.7 % East Asia, 2.5% in west Asia and no relevant updated data was found from central Asian continent. Highest prevalence (10%) of HPV genotype-16 was recorded in Asia among 3, 710 enrolled cases including 2201 males, 1149 females and 360 cases of unknown gender. While undifferentiated multiple HPV genotype prevalence was 5.5 % (204 cases). Lowest percentage of HPV sub-types 68, 72, 57, 39 were recorded respectively. Pakistan ranked top reporting highest number of HPV-16 cases, Taiwan HPV-18, India HPV-31, Japan HPV-35 and Singapore in HPV-16 and HPV-18 co-infection rates respectively. CONCLUSIONS: Exact prevalence of HPV associated head and neck squamous cell carcinomas among Asian population is still debatable. Due to higher heterogeneity (P< 0.00001), I2 = 81-88% at 95 % confidence interval), non-availability and limitations of reported studies from Asian sub-continents especially central Asia, western Asia and from south and south east Asia demand large scale collaborative research culture to standardize head and neck squamous cell carcinomas aetiology.
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Toxicological effects of toxic metals (cadmium and mercury) on blood and the thyroid gland and pharmacological intervention by vitamin C in rabbits.

Cadmium and mercury are non-biodegradable toxic metals that may cause many detrimental effects to the thyroid gland and blood. Vitamin C has been found to be a significant chain-breaking antioxidant and enzyme co-factor against metal toxicity and thus make them less available for animals. The current study was performed to find the effect of individual metals (cadmium and mercury), their co-administration, and the ameliorative effects of vitamin C on some of the parameters that indicate oxidative stress and thyroid dysfunction. Cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1. control; 2. Vit C; 3. CdCl2; 4. HgCl2; 5. Vit C + CdCl2; 6. Vit C + HgCl2; 7. CdCl2 + HgCl2, and 8. Vit C + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. triidothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and triglycerides were measured using commercially available kits. The results exhibited significant decline (p < 0.05) in mean hemoglobin, corpuscular hemoglobin, packed cell volume, T3 (0.4 ± 0.0 ng/ml), and T4 (26.3 ± 1.6 ng/ml) concentration. While, TSH (0.23 ± 0.01 nmol/l) and triglyceride (4.42 ± 0.18 nmol/l) were significantly (p < 0.05) increased but chemo-treatment with Vit C reduces the effects of Cd, Hg, and their co-administration but not regained the values similar to those of controls. This indicates that Vit C had a shielding effect on the possible metal toxicity. The Cd and Hg also found to accumulate in vital organs when measured by atomic absorption spectrophotometer. The metal concentration trend was observed as follows: kidney > liver > heart > lungs. It was concluded that Cd and Hg are toxic and tended to bioaccumulate in different organs and their toxic action can be subdued by vitamin C in biological systems.

The protective role of ascorbic acid in the hepatotoxicity of cadmium and mercury in rabbits.

The liver is one of the vital and sensitive organs which are usually exposed against the toxicity of mercury (Hg) and cadmium (Cd). The main objective of the current study was to evaluate the potential toxicological effects of both Cd and Hg as individual and combined. Hepatotoxicity was evaluated by monitoring the biochemical parameters of the liver and their accumulation in the liver as well as therapeutic role of vitamin C in said toxicity in rabbits (Oryctolagus cuniculus). In this research, cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to treatment groups of the rabbits for 28 alternative days. Various biochemical parameters of the liver such as lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), bilirubin, alanine aminotransferase (ALAT), total protein, and gamma glutamyl transferase (GGT) were estimated using blood samples. Some biochemical parameters like ASAT, ALAT, LDH, GGT, and bilirubin were significantly elevated (P ≤ 0.001) in individual Cd and Hg treatment groups, while the level of total protein was found to be significantly declined. The effects of Cd and Hg in the presence of vitamin C on these biochemical parameters were low as compared to metals-treated groups. Similar results were found when rabbits were treated with co-administration of both metals and vitamin C. Accumulation of Cd and Hg found to be higher in the liver. However, chemoprevention and chemotreatment with vitamin C significantly (P ≤ 0.01) minimized the toxicological effects of both metals but not regained the accumulation similar to that of the control group. The findings of this study provide awareness on accumulation of metals in the liver in rabbits and their toxicity tested through biochemical parameters as well as the therapeutic role of vitamin C in such alterations.

Fabrication of poly (butadiene-block-ethylene oxide) based amphiphilic polymersomes: An approach for improved oral pharmacokinetics of Sorafenib.

Sorafenib (SFN), a hydrophobic anticancer drug, has several limitations predominantly poor aqueous solubility and hepatic first-pass effect, limiting its oral delivery that results into several other complications. Present study aims to develop Sorafenib loaded polymersomes using poly butadiene block poly ethylene oxide (PB-b-PEO), an amphiphilic co-block polymer. Prior to drug loading, critical aggregate concentration (CAC) of polymer was calculated for stable formulation synthesis. The developed SFN loaded PB-b-PEO polymersomes (SFN-PB-b-PEO, test formulation) characterized by DLS and cryo-TEM showed particle size 282 nm, polydispersity (PDI) of less than 0.29 and membrane thickness of about 20 nm. SFN-PB-b-PEO polymersomes demonstrated encapsulation efficiency of 71% and showed sustained drug release up to 144 h. Formulation remained stable for 3 months in suspension form. In vitro cytotoxicity against HepG2 cells showed 1.7 folds improved toxicity compared to SFN suspension. In addition, oral administration of SFN-PB-b-PEO polymersomes in BALB/c mice showed increased Cmax and AUC0-96 by 1.7 and 2.77-fold respectively (p < 0.05) compared to those of SFN suspension (reference formulation). Findings suggest that the SFN-PB-b-PEO polymersomes can be a potential candidate for oral delivery of SFN.

Current state and prospects of the phytosynthesized colloidal gold nanoparticles and their applications in cancer theranostics.

The design, development, and biomedical applications of phytochemical-based green synthesis of biocompatible colloidal gold nanoparticles (AuNPs) are becoming an emerging field due to several advantages (safer, eco-friendly, simple, fast, energy efficient, low-cost, and less toxic) over conventional chemical synthetic procedures. Biosynthesized colloidal gold nanoparticles are remarkably attractive in several biomedical applications including cancer theranostics due to small size, unusual physico-chemical properties, facile surface modification, high biocompatibility, and numerous other advantages. Of late, several researchers have investigated the biosynthesis and prospective applications (diagnostics, imaging, drug delivery, and cancer therapeutics) of AuNPs in health care and medicine. However, not a single review article is available in the literature that demonstrates the anti-cancer potential of biosynthesized colloidal AuNPs with detailed mechanistic study. In the present review article, we for the first time discuss the biointerface of colloidal AuNPs, plants, and cancer mainly (i) comprehensive mechanistic aspects of phytochemical-based synthesis of AuNPs; (ii) proposed anti-cancer mechanisms along with biomedical applications in diagnostics, imaging, and drug delivery; and (iii) key challenges for biogenic AuNPs as future cancer nanomedicine.

Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics.

With the development of the latest technologies, scientists are looking to design novel strategies for the treatment and diagnosis of cancer. Advances in medicinal plant research and nanotechnology have attracted many researchers to the green synthesis of metallic nanoparticles due to its several advantages over conventional synthesis (simple, fast, energy efficient, one pot processes, safer, economical and biocompatibility). Medicinally active plants have proven to be the best reservoirs of diverse phytochemicals for the synthesis of biogenic silver nanoparticles (AgNPs). In this review, we discuss mechanistic advances in the synthesis and optimization of AgNPs from plant extracts. Moreover, we have thoroughly discussed the recent developments and milestones achieved in the use of biogenic AgNPs as cancer theranostic agents and their proposed mechanism of action. Anticipating all of the challenges, we hope that biogenic AgNPs may become a potential cancer theranostic agent in the near future.