From seeds to survival rates: investigating Linum usitatissimum’s potential against ovarian cancer through network pharmacology

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan–Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Development, Statistical Optimization and Characterization of Fluvastatin Loaded Solid Lipid Nanoparticles: A 32 Factorial Design Approach

The purpose of the present research work was to design, optimize, and evaluate fluvastatin-loaded solid lipid nanoparticles (FLV-SLNPs) using 32 factorial design for enhancing the bioavailability. Fluvastatin has several disadvantages, including the low solubility and substantial first-pass metabolism resulting in a low (30%) bioavailability and a short elimination half-life. FLV-SLNPs were prepared using the nano-emulsion technique. For the optimization of the FLV-SLNPs, a total of nine formulations were prepared by varying two independent factors at three levels, using full factorial design. In this design, lipid (A) and surfactant (B) concentrations were chosen as independent factors, whereas entrapment efficiency (Y1) and in-vitro drug release (Y2) were selected as the dependent variables. Additionally, the prepared SLNPs were characterized for X-ray diffraction, Fourier transform-infrared spectroscopy, and differential scanning calorimetry. These studies revealed that there were no interactions between the drug and the selected excipients and the selected formulation components are compatible with the drug. Pharmacokinetic studies in rats confirmed significant improvement in AUC and MRT of SLNPs in comparison with the pure drug indicating the enhanced bioavailability of SLNPs. This study provides a proof-of-concept for the fact that SLNPs can be effectively developed via experimental factorial design, which requires relatively minimal experimentation

A detailed analysis of synonymous codon usage in human bocavirus

AbstractHuman bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory and gastroenteric infections inchildren. To date, four distinct subtypes have been identified worldwide. HBoV1 is the most frequently detected bocavirusin clinical samples derived from the respiratory tract. HBoV has a single-stranded DNA genome, which encodes two nonstructuralproteins, NS1 and NP1, and two structural proteins, VP1 and VP2. Despite a large number of available HBoVsequences, the molecular evolution of this virus remains enigmatic. Here, we applied bioinformatic methods to measure thecodon usage bias in 156 HBoV genomes and analyzed the factors responsible for preferential use of various synonymouscodons. The effective number of codons (ENC) indicates a highly conserved, gene-specific codon usage bias in the HBoVgenome. The structural genes exhibit a higher degree of codon usage bias than the non-structural genes. Natural selectionemerged as dominant factor influencing the codon usage bias in the HBoV genome. Other factors that influence the codonusage include mutational pressure, gene length, protein properties, and the relative abundance of dinucleotides. The resultspresented in this study provide important insight into the molecular evolution of HBoV and may serve as a primer for HBoVgene expression studies and development of safe and effective vaccines to prevent infection

An Effective Delivery System of Sitagliptin Using Optimized Mucoadhesive Nanoparticles

Sitagliptin (MK-0431), is a potent oral hypoglycemic drug that is used for treating type 2 diabetes mellitus. However, the short half-life of sitagliptin requires patients to take a high dose of 50 mg twice per day, and the fraction of sitagliptin reversibly bound to plasma proteins is as low as 38%. In addition, it was reported that approximately 79% of sitagliptin is excreted unchanged in the urine for elimination without metabolism. Thus, a better delivery system is needed to improve the benefits of sitagliptin in patients. The drug content and percentage yield were found to be 73 ± 2% and 92 ± 2%, respectively. The optimized sitagliptin nanoparticle sizes were between 350–950 nm, and the surfaces were smooth and nearly spherical in shape. In addition, the optimized sitagliptin nanoparticles have an indicated excellent bioadhesion property of (6.1 ± 0.5 h). The swelling of the nanoparticles is 168 ± 15%. The pattern of sitagliptin release from the mucoadhesive nanoparticles follows the Korsmeyer-Peppas model. More importantly, the extended sitagliptin retention time, of up to 12 h in the gastrointestinal tract, suggests that the optimized mucoadhesive nanoparticle formulation is more efficient, and has a greater potential to be used for oral delivery compared to the conventional sitagliptin administration in the drug solution. This is the first developed delivery system using the optimized mucoadhesive nanoparticles to enhance the effectiveness of sitagliptin

Improved Renoprotection in Diabetes with Combination Therapy of Coccinia indica Leaf Extract and Low-Dose Pioglitazone

Background: The metabolic changes associated with diabetes can lead to nephropathy eventually resulting in end-stage renal disease. Current antidiabetic therapies do not effectively prevent the onset of diabetic kidney diseases as well as progression. Aim: To evaluate the effect of Coccinia indica leaf extract alone and in combination with pioglitazone, an antihyperglycemic agent was used to modulate the progressive kidney damage induced by type 2 diabetes in rats. Hypotheses: Pioglitazone causes severe adverse effects when administered for long-term therapy. The hypotheses in this study is to examine the renoprotective effect of Coccinia indica leaf extract (200 mg/kg p.o.) when co-administered with low-dose pioglitazone (7 mg/kg) in type-2-diabetes-induced nephropathy in rats and simultaneously evaluate the hypoglycemic response as well. Methods: Rats (Males, Sprague Dawley) were kept on a high-fat diet and were given a single dose of streptozotocin (35 mg/kg, i.p.) to induce diabetic nephropathy. Treatment groups received either Coccinia indica leaf extract or pioglitazone or pioglitazone with Coccinia indica extract, fenofibrate, or lisinopril for 7 weeks. Blood glucose, antioxidant status, triglycerides, total cholesterol, creatinine, blood urea nitrogen, and proteinuria levels were estimated and compared with the normal control and disease control (untreated) groups. Results: The untreated diabetic rats showed increased blood glucose levels, lipid profiles, and renal oxidative stress, along with an increase in nephropathy markers such as blood urea nitrogen, creatinine, and proteinuria. Histopathological examination revealed glomerular damage. Combination treatment with Coccinia indica leaf extract and a low dose of pioglitazone normalized the nephropathic markers as well as histopathological changes. Conclusion: Coccinia indica leaf extract when co-administered with a low dose of pioglitazone as antidiabetic therapy showed good glycemic control and a beneficial renoprotective effect. Combination therapy would lower the dose of pioglitazone and also protect kidneys from drug-induced toxicity as observed from normalized nephropathic markers in a diabetic rat model

Development of a Low-Cost Biomass Furnace for Greenhouse Heating

The energy crisis and increasing fossil fuel prices due to increasing demands, controlled supplies, and global political unrest have adversely affected agricultural productivity and farm profitability across the globe and Pakistan is not an exception. To cope with this issue of energy deficiency in agriculture, the best alternate strategy is to take advantage of biomass and solid waste potential. In low-income countries such as Pakistan, the greenhouse heating system mostly relies on fossil fuels such as diesel, gasoline, and LPG. Farmers are reluctant to adopt greenhouse farming due to the continuously rising prices of the fossil fuels. To reduce reliance on fossil fuel energy, the objective of this study was to utilize biomass from crop residues to develop an efficient and economical biomass furnace that could heat greenhouses to protect the crop from seasonal temperature effects. Modifications made to the biomass furnace, such as the incorporation of insulation around the walls of the furnace, providing turbulators in fire tubes, and a secondary heat exchanger (heat recovery system) in the chimney, have increased the thermal efficiency of the biomass furnace by about 21.7%. A drastic reduction in hazardous elements of flue gases was observed due to the addition of a water scrubber smoke filter in the exit line of the flue. The efficiency of the biomass furnace ranged from 50.42% to 54.18%, whereas the heating efficiency of the diesel-fired heater was 71.19%. On the basis of the equal heating value of the fuels, the unit material and operating costs of the biomass furnace for wood, cotton stalks, corn cobs, and cow dung were USD 2.04, 1.86, 1.78, and 2.00 respectively against USD 4.67/h for the diesel heater. The capital and operating costs of the biomass furnace were about 50% and 43.7% of the diesel heater respectively, resulting in a seasonal saving of about 1573 USD. The produced smoke was tested as environmental friendly under the prescribed limits of the National Environmental Quality Standards (NEQS), which shows potential for its large-scale adoption and wider applications

Enhancement of Anticorrosive Performance of Cardanol Based Polyurethane Coatings by Incorporating Magnetic Hydroxyapatite Nanoparticles

The present investigation demonstrates renewable cardanol-based polyol for the formulation of nanocomposite polyurethane (PU) coatings. The functional and structural features of cardanol polyol and nanoparticles were studied using FT-IR and 1H NMR spectroscopic techniques. The magnetic hydroxyapatite nanoparticles (MHAPs) were dispersed 1&ndash;5% in PU formulations to develop nanocomposite anticorrosive coatings. An increase in the strength of MHAP increased the anticorrosive performance as examined by immersion and electrochemical methods. The nanocomposite PU coatings showed good coating properties, viz., gloss, pencil hardness, flexibility, cross-cut adhesion, and chemical resistance. Additionally, the coatings were also studied for surface morphology, wetting, and thermal properties by scanning electron microscope (SEM), contact angle, and thermogravimetric analysis (TGA), respectively. The hydrophobic nature of PU coatings increased by the addition of MHAP, and an optimum result (105&deg;) was observed in 3% loading. The developed coatings revealed its hydrophobic nature with excellent anticorrosive performance

Differential Effect of Heat Stress on Drought and Salt Tolerance Potential of Quinoa Genotypes: A Physiological and Biochemical Investigation

Soil salinity, drought, and increasing temperatures are serious environmental issues that drastically reduce crop productivity worldwide. Quinoa (Chenopodium quinoa Willd) is an important crop for food security under the changing climate. This study examined the physio-biochemical responses, plant growth, and grain yield of four quinoa genotypes (A7, Titicaca, Vikinga, and Puno) grown in pots containing normal (non-saline) or salt-affected soil exposed to drought and elevated-temperature treatments. Combinations of drought, salinity, and high-temperature stress decreased plant growth and yield more than the individual stresses. The combined drought, salinity, and heat stress treatment decreased the shoot biomass of A7, Puno, Titicaca, and Vikinga by 27, 36, 41, and 50%, respectively, compared to that of control plants. Similar trends were observed for grain yield, chlorophyll contents, and stomatal conductance. The combined application of these three stresses increased Na concentrations but decreased K concentrations in roots and shoots relative to control. Moreover, in the combined salinity, drought, and high-temperature treatment, A7, Puno, Titicaca, and Vikinga had 7.3-, 6.9-, 8-, and 12.6-fold higher hydrogen peroxide contents than control plants. All four quinoa genotypes increased antioxidant enzyme activities (CAT, SOD, and POD) to overcome oxidative stress. Despite A7 producing the highest biomass under stress, it did not translate into increased grain production. We conclude that Puno and Titicaca are more tolerant than Vikinga for cultivation in salt-affected soils prone to drought and heat stress