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Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. A number of trials have demonstrated that statins therapy as well as angiotensin converting enzyme inhibitors is associated with improvements in endothelial function in diabetes. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes. In the present review we provide the up to date details on this subject.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

Endothelial dysfunction is a well established response to cardiovascular risk factors and precedes the development of atherosclerosis. Endothelial dysfunction is involved in lesion formation by the promotion of both the early and late mechanisms of atherosclerosis including up-regulation of adhesion molecules, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, platelet activation, cytokine elaboration, and vascular smooth muscle cell proliferation and migration. Endothelial dysfunction is a term that covers diminished production/availability of nitric oxide and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. Also, when cardiovascular risk factors are treated the endothelial dysfunction is reversed and it is an independent predictor of cardiac events. We review the literature concerning endothelial dysfunction in regard to its pathogenesis, treatment, and outcome.

Nowadays, scientists are currently attempting to lessen the harmful effects of chemicals on the environment. Stability testing identifies how a drug’s quality changes over time. The current work suggests a first and sustainable differential pulse voltammetry technique for quantifying difluprednate (DIF) as an anti-inflammatory agent in the presence of its alkaline degradation product (DEG). The optimum conditions for the developed method were investigated with a glassy carbon electrode and a scan rate of 100 mV s −1 . The linearity range was 2.0 × 10 −7 –1.0 × 10 −6  M for DIF. DIF was found to undergo alkaline degradation, when refluxed for 8 h using 2.0 M NaOH, and DEG was successfully characterized utilizing IR and MS/MS. The intended approach demonstrated the selectivity for DIF identification in pure, pharmaceutical, and degradation forms. The student’s t-test and F value were used to compare the suggested and reported approaches statistically. The results were validated according to ICH requirements. The greenness of the studied approach was evaluated using the Green Analytical Procedure Index and the Analytical Greenness metric. Additionally, the whiteness features of the proposed approach were examined with the recently released red, green, and blue 12 model, and the recommended strategy performed better than the reported approaches in greenness and whiteness.

Five sustainable and validated UV spectrophotometric methods were developed for analyzing chloramphenicol (CHL) and dexamethasone sodium phosphate (DSP) in pure and ophthalmic dosage forms. CHL was detected by zero order spectra method at 292.0 nm in the range 2.00–32.00 µg/mL with limits of detection (LOD) and quantification (LOQ) of 0.96 and 2.88, respectively. DSP was analyzed using the following four techniques: Induce dual wavelength (IDW), fourier self-deconvolution (FSD), ratio difference (RD), and derivative ratio (DD 1 ). The IDW method used at 239.0 and 254.0 nm with a linearity range of 4.00–40.00 µg/mL with LOD and LOQ values were 0.93 and 2.79, respectively. The FSD approach used at 242.0 nm, with a linearity range of 2.00–32.00 µg/mL and 0.65, 1.95 as values of LOD and LOQ, respectively. In the linearity range of 4.00–32.00 µg/mL, RD and DD 1 are applied. RD is utilized at 225.0–240.0 nm, while DD 1 is carried out at 249.0 nm. Values of LOD and LOQ for RD were 0.70 and 2.10 while for DD 1 were 0.80 and 2.40, respectively. These methods were evaluated for their environmental sustainability and validated according to ICH guidelines, overcoming challenges like spectral overlap and collinearity. Statistical comparisons with published methods revealed no significant differences.

A new drug combination of phenylephrine hydrochloride (PHE) and doxylamine succinate (DOX) has been introduced for treating allergic rhinitis. Stability testing is critical for uncovering degradation routes and assessing the stability of combined drugs. This study illustrates the application of two eco-friendly chromatographic techniques which are reversed phase high-performance liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC), for assessing PHE and DOX when DOX oxidative degradation product (DOX DEG) is present. Using liquid chromatography- mass spectroscopy to identify DOX DEG. The HPLC method produced the best separation with isocratic elution and a mobile phase consists of ethanol and 0.01 M phosphate buffer pH = 5.0 (30: 70, v/v), and it was pumped at 1.0 mL/min. The analytes were measured at 260.0 nm using diode array detector (DAD), and the Xterra C 18 column (100 mm × 4.6 mm × 5 m) used as a stationary phase. The method demonstrated a linear response for DOX and PHE across a concentration range of 5.00 to 100.00 µg/mL. The range for DOX DEG was 5.00 to 30.00 µg/mL. The limits of detection (LOD) were determined to be 1.44 for DOX, 1.59 for PHE, and 0.84 µg/mL for DOX DEG. Correspondingly, the limits of quantification (LOQ) were 4.32, 4.77, and 2.52 µg/mL for DOX, PHE, and DOX DEG, respectively. The separation in HPTLC was accomplished by combining ethanol, methylene chloride, and ammonia 30% in ratio 7:2.5:0.5 (v/v/v) as a developing system. The drugs were then quantitatively determined at wavelengths of 260.0 nm using UV detector. The linearity range was 4.00–26.00 (µg/band) for DOX and PHE while it was 0.50–10.00 (µg/band) for DOX DEG. Values of LOD were 0.65 ,0.76 and 0.16 µg/band for PHE, DOX, DOX DEG, respectively. While1.95,2.28 and 0.48 µg/band were values of LOQ. Per ICH guidelines, two analytical methods were validated and proven to be reliable, reproducible, and selective. Additionally, sustainability assessments confirmed their green credentials and practical applicability.

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins’ receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer.

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, p < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, p = 0.016). Oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) decreased by 32.4% (p = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

Since the 1940s, pesticide-intensive crop protection has sustained food security but also caused pervasive impacts on biodiversity, environmental integrity and human health. Here, we employ a systematic literature review to structurally analyze pest management science in 65 developing countries. Within a corpus of 3,407 publications, we find that taxonomic coverage is skewed towards a subset of 48 herbivores. Simplified contexts are commonplace: 48% of studies are performed within laboratory confines. 80% treat management tactics in an isolated rather than integrated fashion. 83% consider no more than two out of 15 farming system variables. Limited attention is devoted to pest-pathogen or pest-pollinator interplay, trophic interactions across ecosystem compartments or natural pest regulation. By overlooking social strata, the sizable scientific progress on agroecological management translates into slow farm-level uptake. We argue that the scientific enterprise should integrate system complexity to chart sustainable trajectories for global agriculture and achieve transformative change on the ground.

The cubeb plant ( Piper cubeba ) is a medicinal plant widely used to treat various digestive and respiratory tract diseases such as asthma, diarrhea, sore throat, and lungs. This is due to the presence of secondary metabolic compounds in the cubeb plant. Each part of the cubeb plant has medicinal properties apart from the fruit, namely the cubeb leaves. This study aimed to profile the secondary metabolic compounds of sun-dried cubeb leaves. This is because the drying system still depends on the sun. Metabolic compound profile analysis using GC-MS ( Gas Chromatography-Mass Spectrometry ). The method using GC-MS was chosen because many secondary metabolite compounds can be profiled using GC-MS. The profiling result value is taken based on the number of compound match factors >70%. Analysis of metabolic compound results using GC-MS was carried out descriptively. The results of secondary metabolic compound profiling of sun-dried cubeb leaves using 96% ethanol solvent identified 24 compounds and 22 compounds identified with 70% ethanol solvent. The sun-dried cubeb leaves contain various secondary metabolic compounds, including terpenes, alkaloids, and flavonoids, which have potential applications in medicine, food additives, and cosmetics.