A DFT approach for finding therapeutic potential of graphyne as a nanocarrier in the doxorubicin drug delivery to treat cancer.

In the present work, the drug-loading efficacy of graphyne (GYN) for doxorubicin (DOX) drug is investigated for the first time by using density functional theory (DFT). Doxorubicin drug is effective in the cure of numerous types of cancer including bone cancer, gastric, thyroid, bladder, ovarian, breast, and soft tissue cancer. Doxorubicin drug prevents the cell division process by intercalating in the double-helix of DNA and stopping its replication. The optimized, geometrical, energetic, and excited-state characteristics of graphyne (GYN), doxorubicin drug (DOX), and doxorubicin-graphyne complex (DOX@GYN complex) are calculated to see how effective it is as a carrier. The DOX drug interacted with GYN with an adsorption-energy of -1.57 eV (gas-phase). The interaction of GYN with DOX drug is investigated using NCI (non-covalent interaction) analysis. The findings of this analysis showed that the DOX@GYN complex has weak forces of interaction. Charge transfer from doxorubicin drug to GYN during DOX@GYN complex formation is described by charge-decomposition analysis and HOMO-LUMO analysis. The increased dipole-moment (8.41 D) of the DOX@GYN in contrast with therapeutic agent DOX and GYN indicated that the drug will move easily in the biochemical system. Furthermore, the photo-induced electron-transfer process is explored for excited states, and it reveals that upon interaction, fluorescence-quenching will occur in the complex DOX@GYN. In addition, the influence of the positive and negative charge states on the GYN and DOX@GYN is also considered. Overall, the findings indicated that the GYN could be exploited as an effective drug-transporter for the delivery of doxorubicin drug. Investigators will be inspired to look at another 2D nanomaterials for drug transport applications as a result of this theoretical work.

Antioxidant, Anti-Obesity, and Hypolipidemic Effects of Polyphenol Rich Star Anise (Illicium verum) Tea in High-Fat-Sugar Diet-Induced Obesity Rat Model.

Star anise (Illicium verum Hook. fil.) is commonly utilized as a culinary and medicinal fruit and is most famous in indigenous systems of medicine. The present research work aims to appraise and validate the potential of polyphenol-rich star anise tea (SAT) on oxidative stress, obesity and related biochemical parameters in high-fat-sugar-diet (HFSD)-induced obesity model in rats. SAT was prepared using the traditional method in warm water. The Reverse Phase High Pressure Liquid Chromatography (RP-HPLC) analysis was performed for the simultaneous determination of phenolic acids and flavonoids in SAT. Two doses (250 and 500 mg/kg body weight) were selected to investigate the anti-obesity potential of SAT using HFSD-induced obese rat model. Major (>5 mg/100 mL) phenolic acids in SAT were p-coumeric acid, gallic aid, cinamic acid, chlorogenic acid and ferulic acid while catechin and rutin were the major flavonoids detected in the SAT. SAT exhibited 51.3% DPPH radical scavenging activity. In vivo study showed that higher doses of SAT (500 mg/kg body weight) significantly reduced the body weight increase (74.82%) and BMI (0.64 g/cm2). Moreover, significant reductions in the levels of serum total cholesterol, triglyceride, LDL and VLDL were recorded in all the treatment groups in comparison to the HFSDC group. Furthermore, SAT reduced the alterations in MDA, SOD and GSH levels of experimental groups thus showing the potential against oxidative stress. The SAT-500 group showed a significant decrease in the elevated kidney and liver weights and atherogenic index in comparison to the HFSDC group. The present study proved that SAT exhibited strong protective effects against obesity and oxidative stress, especially at higher doses.

Polymorphism association and expression analysis of alpha-lactalbumin (LALBA) gene during lactation in Nili Ravi buffalo.

Alpha-lactalbumin has been reported as a highly polymorphic gene that potentially alters the gene expression and is associated with milk composition in dairy breeds. Current study was conducted in two phases. In the first phase, polymorphisms identification in alpha-lactalbumin (LALBA) gene and its association with milk composition was performed. To identify the genetic polymorphism, Nili Ravi buffaloes at their second lactation were selected from Government livestock farm (Buffalo Research Institute, Pattoki). Genomic DNA was extracted from blood samples. After PCR amplification, products were sequenced, and data was analyzed. Results showed that the identified polymorphisms at chromosomal position 34310940 were found associated with major whey protein. In the second phase of study, milk samples were collected from five healthy mastitis-free Nili Ravi buffaloes in their second lactation for expression analysis of alpha-lactalbumin gene at their transition (day 15), mid (day 90), and late (day 250) lactation. Gene expression was observed highest in transition phase with a gradual decrease of expression in mid and late phase of lactation. Further studies are needed to explore the regulation of milk production genes and their translational efficiency during the course of lactation.

Survival And Progression After Radical Nephrectomy In A Cohort Of Non-Metastatic Renal Cell Carcinoma Treated With Curative Intent.

BACKGROUND: Radical nephrectomy (RN) is a standard treatment of cure for non-metastatic renal cell carcinoma (NMRCC). Long-term outcome data are limited for Pakistani population. Our aim was to assess the long-term outcomes of RCC treated with curative intent with radical nephrectomy (RN) and to study the 5 & 10years survival outcomes in patients with NMRCC who underwent radical nephrectomy. METHODS: This is a retrospective review and analysis of the data between December 2006 and February 2017. We included all the adult patients (age ≥18 years) with NMRCC from both genders irrespective of their histologic subtypes who underwent radical nephrectomy (RN) with a curative intent. The data was analysed for overall survival and recurrence rates at 5- and 10-years using Kaplan-Meier survival analysis. Multivariate analysis was performed using Cox-regression to identify risk factors associated with poor overall outcome in terms of recurrence and mortality. RESULTS: Three hundred and forty-four patients with 195 (55.5%) males and 149 (44.2%) females with a mean age of 53.5±14.1 years were monitored for a mean follow-up of 31.1±26.77 months (range: 3-132 months). Overall there were 46 (13.4%) deaths. Forty-nine 14.2%) cases had disease recurrence with 33 (9.5%) deaths from disease progression. The 5-year progression-free survival was 37% (95% CI: 49.04-72.76) with the median time to recurrence of 33 months (95% CI: 27.6-38.4) and the median overall survival was 103.7 months (95% CI: 95.7-111.7). The 5-year overall survival was 76.1% (95% CI: 75.2-77) while 10-year survival was 70.8%. There was a significant median survival difference for cases with and without recurrence (log-rank χ2: 117.5, p<0.001), T stage, Fuhrman's grade, and early postoperative recurrence. CONCLUSIONS: Radical nephrectomy offers the best survival for nonmetastatic renal cell carcinoma patients with excellent postoperative survival and progression-free profile. Although renal cell cancer presents in younger age group but the long-term survival after radical nephrectomy in Pakistani population is similar to the rest of the world.

Osteopontin gene polymorphism association with milk traits and its expression analysis in milk of riverine buffalo.

Osteopontin gene is regarded as a plausible candidate in mammary gland differentiation and development, expressed by variety of cells, tissues, and biological fluids including milk. The current study was performed in two phases. In the first phase, Osteopontin gene polymorphisms were identified and associated with milk composition such as ash, milk fat, SNF, lactose, and protein. In the second phase, milk samples from five healthy mastitis-free Nili Ravi buffaloes were analyzed for expression of Osteopontin gene at transition (day 15), mid (day 90), and end (day 250) stage of their second lactation. Briefly, blood samples were collected from Nili Ravi buffalo to isolate the genomic DNA, specific primers were designed for PCR amplification. The amplified PCR products were sequenced bi-directionally. Six polymorphisms were identified in the coding region and four in the intronic region of the gene. The results showed that SNP g.38329758 T > C causing substitution of valine to alanine (V127A) was associated with high milk protein. For mRNA expression analysis, somatic cells were separated from milk samples for RNA isolation. Analysis of differential gene expression data has permitted us to illustrate the expression pattern of osteopontin gene in lactating buffalo. The Osteopontin gene was found to be transcribed among all three lactation stages, but expression was observed with the highest value (fold change) in peak lactation and remained elevated till the end of lactation. Identified gene marker may be helpful for the prediction of superior animal for selection. The presented study also gave an insight into the genetic screening and lactation biology of riverine buffalo, offering direction for future research in lactating buffalo.

Charlson Comorbidity Index for Prediction of Outcome of Acute Kidney Injury in Critically Ill Patients.

INTRODUCTION: This study aimed to determine predictors of outcomes in critically ill patients with acute kidney injury (AKI), and to study the impact of the Charlson Comorbidity Index (CCI) as a prognostic indicator. MATERIALS AND METHODS: This retrospective study included critically ill patients who were admitted with AKI or developed AKI during their hospital stay. The impact of comorbidity was evaluated by the CCI, while severity of AKI was assessed by the RIFLE criteria. RESULTS: The mean age of 786 patients with AKI was 59.0 ± 17.0 years (59% men). The most common cause was sepsis in 51% of the patients. In-hospital mortality rate was 42%. The need for mechanical ventilation (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.23 to 3.04), vasoactive drugs (OR, 9.67; 95% CI, 6.35 to 14.73), dialysis (OR, 1.78; 95% CI, 1.14 to 2.78), failure class of RIFLE criteria (OR, 2.02; 95% CI, 1.00 to 4.08), and a CCI greater than 6 (OR, 2.20; 95% CI, 1.38 to 3.52) were independently associated with mortality. At 90 days of follow-up, 6% of the patients were dialysis dependent, while 32% and 62% had partial and complete recovery, respectively. In multivariable analysis, a CCI greater than 6 (OR, 0.47; 95% CI, 0.26 to 0.83), need for dialysis in hospital (OR, 0.31; 95% CI, 0.17 to 0.54), and failure class (OR, 0.19; 95% CI, 0.07 to 0.55) were independent predictors of poor renal outcomes. CONCLUSIONS: The CCI independently predicts in-patient mortality and poor renal outcomes in patients with AKI.