Preparation, characterization and evaluation of HPßCD-PTX/PHB nanoparticles for pH-responsive, cytotoxic and apoptotic properties.

Paclitaxel (PTX) is a potent anticancer drug. However, PTX exhibits extremely poor solubility in aqueous solution along with severe side effects. Therefore, in this study, an inclusion complex was prepared between PTX and hydroxypropyl-ß-cyclodextrin (HPßCD) by solvent evaporation to enhance the drug's solubility. The HPßCD-PTX inclusion complex was then encapsulated in poly-3-hydroxybutyrate (PHB) to fabricate drug-loaded nanoparticles (HPßCD-PTX/PHB NPs) by nanoprecipitation. The HPßCD-PTX/PHB NPs depicted a higher release of PTX at pH 5.5 thus demonstrating a pH-dependent release profile. The cytotoxic properties of HPßCD-PTX/PHB NPs were tested against MCF-7, MDA-MB-231 and SW-620 cell lines. The cytotoxic potential of HPßCD-PTX/PHB NPs was 2.59-fold improved in MCF-7 cells in comparison to free PTX. Additionally, the HPßCD-PTX/PHB NPs improved the antimitotic (1.68-fold) and apoptotic (8.45-fold) effects of PTX in MCF-7 cells in comparison to PTX alone. In summary, these pH-responsive nanoparticles could be prospective carriers for enhancing the cytotoxic properties of PTX for the treatment of breast cancer.

Association of triglyceride glucose index and triglyceride HDL ratio with glucose levels, microvascular and macrovascular complications in Diabetes Mellitus Type-2.

Objective: To find out the role of triglyceride glucose index (TGI) and triglyceride HDL ratio (THR) as predictors of insulin resistance and control of glucose status in type two diabetes mellitus (T2DM). Method: This cross-sectional study was conducted in Dr. Akbar Niazi Teaching Hospital, January-April 2022. A total of 56 individuals, both males and females aged 30-75 years having T2DM with fasting blood glucose ≥ 110 mg/dl and HbA1c ≥ 5.7% were included. Biochemical markers were estimated by applying standard methods. Independent sample t-test, Fisher exact test, and linear regression were applied. Results: TGI and triglyceride HDL ratio were significantly raised (p=0.01) in patients with poor glycemic control as compared to controlled glucose levels (17.8 ± 4.7vs7.3 ± 1.75) and (3.84 ± 1.3vs2.12 ± 0.64) respectively. These two indices have a significant association (p=0.01) with HbA1c (r=0.963, r=0.757), fasting blood glucose (r=0.964, r=0.748), and HOMA-IR (r=0.955, r=0.718) respectively. Moreover, TGI and THR were found to have a more significant association with the development of cardiovascular disease (CVD) (r=0.717, r=0.555) and a significant but weak association with nephropathy (r=0.385, r=0.302) respectively. Regression analysis revealed that both TGI and THR have significant predictive ability for HbA1c, fasting blood glucose, HOMA-IR and CVD (delta R2=0.738vs 0.408, 0.740vs0.395, 0.725vs0.362, 0.354vs0.170) respectively, after controlling all confounding variables. Conclusions: TGI and THR have a strong association and predictive capability to identify insulin resistance and detect the development and progression of T2DM. Moreover, TGI can be more precisely used for prediction analysis as compared to THR.

Multidisciplinary Integrated Care in Atrial Fibrillation (MICAF): A Systematic Review and Meta-Analysis.

Objective: To assess the effectiveness of multidisciplinary integrated care in the clinical outcomes of atrial fibrillation patients.Methods: Medline, EMBASE, and the CENTRAL trials registry of the Cochrane Collaboration were searched for articles on multidisciplinary integrated care in atrial fibrillation patients. The systematic review and meta-analysis included six and five articles, respectively, that compared the outcomes between the integrated care group and control group.Results: Multidisciplinary integrated care was concomitant with a decrease in all-cause mortality (OR 0.52, 95%CI 0.36-0.74, P=0.0003) and cardiovascular hospitalization (OR 0.66, 95%CI 0.49-0.89, P=0.007). Multidisciplinary integrated care had no significant impact on major adverse cardiovascular event (MACE) (OR 0.76, 95%CI 0.37-1.53, P=0.44), cardiovascular deaths (OR 0.49, 95% CI 0.21-1.17, P=0.11), atrial fibrillation (AF)-related hospitalization (OR 0.76, 95%CI 0.53-1.09, P=0.14), major bleeding (OR 1.02, 95%CI 0.59-1.75, P=0.94), minor bleeding (OR 1.12, 95%CI 0.55-2.26, P=0.76), and cerebrovascular events (OR 0.72, 95%CI 0.45-1.18, P=0.19).Conclusion: In comparison to usual care, a multidisciplinary integrated care approach (i.e., nurse-led care along with usual specialist care) in AF patients is associated with reduced all-cause mortality and cardiovascular hospitalization.

Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats.

BACKGROUND AND PURPOSE: Despite many liver disorders, clinically useful drugs are scarce. Moreover, the available therapies are facing the challenges of efficacy and safety. Alhagi camelorum has been used in folk medicine globally for millennia to treat several ailments. Alhagi camelorum (Ac) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. Our goal was to determine the hepatoprotective activity of Alhagi camelorum against valproic acid induced hepatotoxicity using an animal model. EXPERIMENTAL APPROACH: The animals were segregated in 4-groups (6 male rats each) weighing 250-290 g. Group-1 animals were treated with normal saline, Group-2 animals were treated with VPA at the dose of 500 mg/kg i.p for 14 days consecutively, while Group-3 and 4 were treated with valproic acid (VPA) at the dose of 500 mg/kg i.p for 14 days along with 400 mg/kg and 600 mg/kg of Ac hydroalcoholic extract respectively. Subsequently, blood serum samples and liver tissues were collected for biochemical and histopathological analysis. Phytochemical screening was carried out to screen for phytochemical classes and HPLC analysis was conducted to screen polyphenols. The antioxidant activity was carried by different assays such as DPPH, SOD, NO etc. KEY RESULTS: The administration of Ac showed hepatoprotection at the doses of 400 and 600 mg/kg. Ac significantly reduces the elevated serum levels of liver biomarkers compared to the valproic acid-induced hepatotoxic group. These findings were confirmed with histopathological changes where Ac was capable of reversing the toxic effects of valproic acid on liver cells CONCLUSION: It is concluded that Ac showed significant hepatoprotective effects at different doses in the animal model used in this study.

Hyperglycemia-associated Alzheimer's-like symptoms and other behavioral effects attenuated by Plumeria obtusa L. Extract in alloxan-induced diabetic rats.

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person's physical and psychological health. Plumeria obtusa L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior. Plumeria is a genus with antipsychotic activities. The objective of this study was to examine the effects of a methanolic extract of Plumeria obtusa L. in the attenuation of diabetes, on symptoms of Alzheimer disease, and on other associated behavioral aspects. A single dose of alloxan was administered to an experimental group of rats to induce development of diabetes (150 mg/kg, intraperitoneal) and the rats were then administered selected doses of methanolic extract of Plumeria obtusa L. (Po.Cr) or glibenclamide (0.6 mg/kg) for 45 consecutive days. Behavioral effects were evaluated using three validated assays of anxiety-related behavior: the open field test, the light and dark test, and the elevated plus maze. Anti-depressant effects of Plumeria obtusa L. were evaluated using the forced swim test (FST) and memory and learning were assessed using the Morris water maze (MWM) task. Po.Cr was also evaluated for phytochemicals using total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography assays, and antioxidant capability was assessed through assays of DPPH radical scavenging, total oxidation capacity, and total reducing capacity. In the alloxan-induced model of diabetes, the administration of Po.Cr and glibenclamide for 45 days produced a marked decrease (p < 0.001) in hyperglycemia compared to control animals. Po.Cr treatment also resulted in improvement in indicators, such as body weight and lipid profile (p < 0.05), as well as restoration of normal levels of alanine transaminase (ALT) (p < 0.001), a biomarker of liver function. Diabetic rats presented more Alzheimer-like symptoms, with greater impairment of memory and learning, and increased anxiety and depression compared to non-diabetic normal rats, whereas treated diabetic rats showed significant improvements in memory and behavioral outcomes. These results demonstrate that Po.Cr reversed alloxan-induced hyperglycemia and ameliorated Alzheimer-related behavioral changes, which supports additional study and assessment of conventional use of the plant to treat diabetes and associated behavioral complications.

Trends of Antimicrobial Resistance in Typhoidal Strains of Salmonella in a Tertiary Care Hospital in Pakistan.

INTRODUCTION: Enteric fever or typhoid fever is a major public health issue affecting greater than 27 million individuals globally and is responsible for greater than 200,000 deaths per year. Due to the extensive overuse of antimicrobials, the world is moving toward a pre-antibiotic era. The emergence and transmission of antibiotic-resistant Salmonella species are a global threat and a serious concern in developing countries such as Pakistan. This study aimed to determine the trends in antimicrobial resistance (AMR) of typhoidal strains of Salmonella in a tertiary care hospital in Pakistan. MATERIALS AND METHODS: It was a descriptive, cross-sectional study conducted in the pathology department of Sharif City Hospital, Lahore, after approval by the ethical committee of the institution. A total of 50 blood culture specimens positive for Salmonella typhi and Salmonella paratyphi from January 2019 to March 2020 were included by the non-probability consecutive sampling technique. The samples were processed by conventional bacteriological methods for isolation and identification. The antimicrobial susceptibility testing was done by the Kirby-Bauer disc diffusion method as recommended by the Clinical and Laboratory Standard Institute (CLSI). The statistical package for social sciences (SPSS, IBM Corp., Armonk, NY) version 25 was used for data entry and analysis. RESULTS: Among the first-line drugs (ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole), 70% of strains were resistant, and only 30% strains were sensitive to them. Among the cephalosporins, 52% strains were sensitive to ceftriaxone, and 48% strains were sensitive to ceftazidime, cefotaxime, and cefepime. Twenty-four percent of strains were sensitive to ciprofloxacin. Only 50% of strains were sensitive to ampicillin-sulbactam, and 92% of strains were sensitive to piperacillin-tazobactam. All the strains were 100% sensitive to imipenem and meropenem; 96% of strains were sensitive to co-amoxiclav, doxycycline, and azithromycin. The frequency of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Salmonella species was 16% and 54%. CONCLUSION: The increasing frequency of MDR and XDR Salmonella species in Pakistan is a major concern. A significant percentage of the typhoidal strains of Salmonella is resistant to the first-line (16%) and second-line (54%) antibiotics. Carbapenems and azithromycin are the last resort of therapy in such cases.

Infective endocarditis post-transcatheter aortic valve implantation (TAVI), microbiological profile and clinical outcomes: A systematic review.

BACKGROUND: The data on infective endocarditis after transcatheter aortic valve implantation (TAVI) is scarce and limited to case reports and case series in the literature. It is the need of the hour to analyze the available data on post-TAVI infective endocarditis from the available literature. The objectives of this systematic review were to evaluate the incidence of infective endocarditis after transcatheter aortic valve implantation, its microbiological profile and clinical outcomes. It will help us to improve the antibiotic prophylaxis strategies and treatment options for infective endocarditis in the context of TAVI. METHODS: EMBASE, Medline and the CENTRAL trials registry of the Cochrane Collaboration were searched for articles on infective endocarditis in post-TAVI patients till October 2018. Eleven articles were included in the systematic review. The outcomes assessed werethe incidence of infective endocarditis, its microbiological profile andclinical outcomes including major adverse cardiac event (MACE), net adverse clinical event (NACE), surgical intervention and valve-in-valve procedure. RESULTS: The incidence of infective endocarditis varied from 0%-14.3% in the included studies, the mean was3.25%. The average duration of follow-up was 474 days (1.3 years). Enterococci were the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus (16.1%) and coagulase-negative Staphylococcus species (14.7%). The mean in-hospital mortality and mortality at follow-up was 29.5% and 29.9%, respectively. The cumulative incidence of heart failure, stroke and major bleeding were 37.1%, 5.3% and 11.3%,respectively. Only a single study by Martinez-Selles et al. reported arrhythmias in 20% cases. The septic shock occurred in 10% and 27.7% post-TAVI infective endocarditis patients according to 2 studies. The surgical intervention and valve-in-valve procedure were reported in 11.4% and 6.4% cases, respectively. CONCLUSION: The incidence of post-TAVI infective endocarditis is low being 3.25% but it is associated with high mortality and complications. The most common complication is heart failure with a cumulative incidence of 37.1%. Enterococciare the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus in 16.1% of cases. Appropriate measures should be taken to prevent infective endocarditis in post-TAVI patients including adequate antibiotics prophylaxis directed specifically against these organisms. STUDY REGISTRATION: PROSPERO registration number CRD42018115943.

Cloning, Genetic Transformation and Cellular Localization of Abiotic Stress Responsive Universal Stress Protein Gene (GUSP1) in Gossypium hirsutum.

BACKGROUND: Drought stress seriously affects the cotton fiber development. Universal stress protein gene isolated from native species Gossypium arboreum has the promising tolerance role against these stresses. OBJECTIVES: This study aimed to clone, characterize, and genetically transform the GUSP1 gene in local cotton and to observe its expression in transgenic plants under drought stress. MATERIALS AND METHODS: Universal Stress Protein (GUSP1) gene from Gossypium arboreum was cloned in pCEMBIA (-) 1301plant expression vector by replacing Hygromycin and GUS exon with GUSP1-GFP fusion fragment. The construct was transformed into Agrobacterium tumefaciens and transient expression assay was confirmed by agro-infiltration of Nicotiana benthamiana leaves and green fluorescence under a confocal microscope. Gene integration and expression in transgenic plants was observed through Southern blot and real-time PCR analyses. Cellular localization was observed through a confocal microscope and the copy number of the transgene was observed in progeny plants. RESULTS: Transformation efficiency was 1.9%. Developmental and spatial expression of GUSP1 was observed through Real-time PCR in stem, root, leaf, inflorescence, and seeds of transgenic plants at the vegetative and flowering stage. Integration of GUSP1 revealed a fragment of approximately 500 bp in Southern Blot analyses. Localization of GUSP1 was detected in the intact leaf of transgenic plants through GFP fluorescence in midrib, guard cells of stomata, and trichomes. Single gene copy was detected in the chromosome of transgenic seeds. CONCLUSION: GUSP1 has cloned from native species of local cotton and its integration and expression in transgenic plants confirmed that the role of GUSP1 will provide direction to breed economically important cotton varieties.