Explore the vast range of titles available.

Olfactory dysfunction has emerged as an important clinical issue, particularly following the global rise in post-viral anosmia. Recent research suggests an association between altered calcium homeostasis and poor olfactory signaling, but there is no validated method for assessing calcium levels in nasal secretions. Herein, a novel paper-based electrochemical sensor for the direct determination of free calcium ions in nasal secretions, providing potential diagnostic biomarker in olfactory dysfunction. The sensor integrates multi-walled carbon nanotubes, carbon dots synthesized from guava fruit, and the calcium-selective ionophore ETH 1001 to improve conductivity and selectivity. It exhibits a Nernstian response with a slope of 29.14 ± 0.3 mV/decade over a linear range from 10 −7 to 10 −1  M, and a detection limit of 7.5 × 10 −8  M. The sensor has good consistency, with less than 1 mV fluctuation in potential over 180 days, and strong selectivity against interfering nasal electrolytes. Applied to nasal samples from 166 participants, the sensor demonstrated significantly elevated calcium levels in patients with anosmia compared to healthy controls (7.30 ± 0.004 × 10⁻ 2  M vs. 1.84 ± 0.01 × 10⁻ 2  M, p  < 0.05). Compared to existing technologies, the proposed sensor achieves superior sensitivity, broader linearity, and greater pH tolerance.

Previously developed fluorophenyl-isoxazole-carboxamides derivatives were re-synthesized and their scavenging activity against DPPH free radical and inhibitory activity against lipase and α-amylase enzymes were evaluated. The inhibition of the tested enzymes was weak while the most potent activities were observed in the DPPH assay. In particular, compounds 2a and 2c demonstrated high antioxidant potency with IC 50 values of 0.45 ± 0.21 and 0.47 ± 0.33 µg/ml, respectively, when compared to Trolox, the positive control compound, which has an IC 50 value of 3.10 ± 0.92 µg/ml. Based on the in vitro results, the most potent compound 2a was chosen for in vivo evaluation of antioxidant properties using 20 male mice injected intra-peritoneally and divided into four groups. The in vivo results revealed that total antioxidant capacity (TAC) obtained for mice treated with 2a was two folds greater than that of mice treated with the positive control Quercetin. Although further biological and preclinical investigations need to be performed to assess the therapeutic potential of 2a , the results of this study show promising antioxidant activities both in vitro and in vivo.

Series of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. These series of derivatives were synthesized by different reactions like Vilsmeier–Haack reaction and click reaction. In vitro COX-1 and COX-2 inhibition studies showed that five compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 values in 0.551–0.002 μM range. In the diarylpyrazole derivatives, compound 4b showed the best inhibitory activity against COX-2 with IC50 = 0.017 μM as one of the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, when the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone (compound 4d), best COX-2 selectivity was achieved (IC50 = 0.098 μM, SI = 54.847). In the diaryltriazole derivatives, compound 15a showed the best inhibitory activity in comparison to all synthesized compounds including the reference celecoxib with IC50 = 0.002 μM and SI = 162.5 as it could better fit the extra hydrophobic pocket which is present in the COX-2 enzyme. Moreover, the docking study supports the obtained SAR data and binding similarities and differences on both isozymes.

Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Bill & Melinda Gates Foundation.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3·5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

Background Aloysia citriodora Palau (AC) is commonly known as Lemon Verbena and has been utilized as a medicinal tea in folkloric medicine for the treatment of abdominal spasm, anxiety, and fever. The present investigation aimed to identify the chemical ingredients of AC essential oil (EO) collected from two different locations in Palestine and to assess their antioxidant, antimicrobial, cytotoxic, and cyclooxygenase (COX) inhibitory effects. Methods Gas chromatography/mass spectroscopy (GC/MS) technique was used to identify the chemical components of the hydro-distilled EO from both regions, while DPPH, MTS, and COX assays were utilized to estimate the antioxidant, cytotoxic, and COX inhibitory activities of the EOs, respectively. Moreover, a broth microdilution assay was used to assess antimicrobial potentials against seven microbial strains. Results The GC/MS technique revealed the presence of 17 compounds from the AC collected from the Umm al-Fahm region and 13 compounds from the sample from the Baqa al-Gharbiyye region, while α-citral was the major component of both EOs, representing 47.62 and 43.46%, respectively. The Baqa al-Gharbiyye AC EO exerted more potent antioxidant activity than the Umm al-Fahm EO, with IC 50 values of 11.74 ± 0.18 and 35.48 ± 0.14 μg/mL, respectively, while the positive control Trolox had antioxidant IC 50 values of 2.45 ± 0.01 μg/mL. Interestingly, both EOs inhibited more potential activity against Methicillin-Resistant Staphylococcus aureus (MRSA) and Proteus vulgaris than Ciprofloxacin and Ampicillin antibiotics and also showed more potent antifungal activity against Candida albicans than Fluconazole. Moreover, the Baqa al-Gharbiyye AC EO had a more potent cytotoxic effect than the Umm al-Fahm EO, with IC 50 values of 84.5 ± 0.24 and 33.31 ± 0.01 μg/mL, respectively, compared with Doxorubicin, which had an IC 50 dose of 22.01 ± 1.4 μg/mL. The EOs from Baqa al-Gharbiyye showed potent activity against both COX-1 and COX-2 enzymes, with IC 50 of 52.93 ± 0.13 and 89.31 ± 0.21 μg/mL, respectively, while the EOs from the Umm al-Fahm region showed weaker activity against these enzymes, with IC 50 of 349.99 ± 0.33 and 1326.37 ± 1.13 μg/mL, respectively. Conclusion Both characterized EOs have a huge variety of chemical components. The Baqa al-Gharbiyye AC EO has more potent antioxidant and cytotoxic activities than the Umm al-Fahm EO, but both have potential antimicrobial activity against MRSA, P. vulgaris, and C. albicans. These results suggest the use of AC EOs as promising sources of active ingredients in the food, cosmetic, and pharmaceutical industries.

Introduction. In traditional medicine, many pharmacological activities have already been ascribed to the genus of Teucrium plant. These include antirheumatic antispasmodic, anthelmintic, diuretic, hypoglycemic, and anticancer effects. The recent investigation aimed to characterize and estimate the chemical composition, anti-inflammatory, antioxidant, and anticancer potentials of the essential oil isolated by the microwave-ultrasonic apparatus from Teucrium pruinosum leaves collected from Palestine. Methods. The essential oil (EO) was analyzed by Gas Chromatography equipped with mass spectrometry (GC-MS), while its anticancer activity was evaluated against HeLa cervical adenocarcinoma cells. The ability of T. pruinosum EO to inhibit the conversion of Arachidonic Acid (AA) to PGH2 by ovine COX-1 and human recombinant COX-2 was determined using a COX inhibitor screening assay. In addition, the antioxidant activity of the EO was evaluated on the basis of the scavenging activity with a stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, while Trolox was used as a positive control. Results. Forty-four molecules were identified in T. pruinosum EO, representing 100% of the total EO. Agarospirol was found to be the most abundant component (45.53%) followed by caryophyllene (19.35%). However, the cyclooxygenase inhibitor assay revealed that T. pruinosum has potential COX-1 and Cox-2 inhibitory activity with IC50 values of 0.25 µg/ml and 0.5 µg/ml, respectively. Moreover, the T. pruinosum EO showed moderate antioxidant capacity with an IC50 value of 16.98±0.84 µg/ml in comparison with the positive control Trolox, which has an antioxidant potential with an IC50 value of 2.09±0.17 µg/ml. In addition, 250, 125, 62.5, 31.25, 15.625, 7.67, and 3.84 mg/ml of T. pruinosum EO treatments inhibited mitochondrial activity (cell viability) significantly and extremely by 90-95%. Conclusion. The current study provided data that revealed that the T. pruinosum EO could be a suitable candidate for use as a novel anticancer, anti-inflammatory, and antioxidant medication. Further clinical trials would be required to ensure these effects and to allow the design of suitable pharmaceutical dosage forms from this natural oil.

Pellitory plant (Parietaria judaica (PJ)) is one of the most widely used Arabian traditional medicinal plants due to its ability to cure several infectious diseases and other illnesses. The current study is aimed at assessing the phytoconstituents, antilipase, antiamylase, antimicrobial, and cytotoxic characters of the Pellitory plant (Parietaria judaica (PJ)). Phytochemical screening and procyanidin detection were conducted according to the standard phytochemical procedures. Porcine pancreatic lipase and α-amylase inhibitory activities were carried out using p-nitrophenyl butyrate and dinitrosalicylic acid assays, respectively. In addition, antimicrobial activity was determined utilizing a microdilution assay against several bacterial and fungal strains. Besides, the cytotoxic effect against HeLa cell line was tested employing 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The quantitative test results revealed that the methanol fraction of PJ contains 18.55±0.55 mg of procyanidin and has a potential α-amylase inhibitory activity compared with the antidiabetic drug Acarbose with IC50 values of 15.84±2.25 and 28.18±1.22 μg/ml, respectively. Also, it has a potential antilipase activity compared to the commercial antiobesity drug, Orlistat, with IC50 values of 38.9±0.29 and 12.3±0.35 μg/ml, respectively. The acetone, hexane, and methanol fractions have broad-spectrum antibacterial activity against the screened bacterial strains, while the acetone fraction has shown anticandidal activity with a MIC value of 0.195 mg/ml. The PJ hexane and acetone fractions decreased HeLa cell viability significantly (p value < 0.0001) by approximately 90% at the concentration of 0.625 mg/ml. The revealed outcomes showed that the methanol fraction has strong α-amylase and lipase inhibitory characters. Besides, acetone, hexane, and methanol fractions have broad-spectrum antibacterial activity, while the acetone fraction revealed potent antifungal activity against Candida albicans. Moreover, at low concentrations, hexane and acetone fractions have potent cytotoxic and antiproliferative activity against HeLa cancer cells. Nevertheless, PJ acetone, hexane, and methanol fractions can serve as an effective source of natural products to develop new antiobesity, antidiabetic, antimicrobial, and anticancer agents.

Laurus nobilis (LN) has been used throughout the years as a food flavoring and in traditional medicine. The LN leaves have various biological activities, such as antioxidant, wound healing, antibacterial, analgesic, and anti-inflammatory activities. However, oxidative stress, cancer, diabetes, microbial infections, and inflammatory diseases are closely linked. The objective of this research is to characterize Laurus nobilis (LN) aromatic oil (AO) and evaluate its antioxidant, antidiabetic, antiobesity, antimicrobial, and antimutagenic bioactivities. The AO constituents were characterized using gas chromatography–mass spectrometry (GC–MS). The antimicrobial activity was performed using a microdilution assay against six common microbial species. Free radicals, a porcine pancreatic lipase, α-amylase, and α-glucosidase inhibitory assays were conducted utilizing reference biomedical methods. The cytotoxic effect of LNAO was established on a variety of cancer and normal cell lines using the MTS assay. The anti-inflammatory activity of LNAO was evaluated using the Cayman COX activity kit. The results indicate about 99% of the total oil is composed of 36 compounds, the characterized AO metabolites showed content of many oxygenated terpenoids with 1,8-Cineole and Terpinyl acetate as a major component with a percentage of (40.39 and 15.07, respectively. The plant AO showed potent antioxidant activity (IC50 = 2.2 ± 1.38) and has moderate anti-amylase (IC50 = 60.25 ± 1.25), anti-glucosidase (IC50 = 131.82 ± 0.1), and antilipase (IC50 = 83.17 ± 0.06) activities. Moreover, LNAO showed potent antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Proteus vulgaris (MICs = 1.56 µg/mL), methicillin-resistant Staphylococcus aureus (MRSA) (MIC = 3.125 µg/mL) and Candida albicans (MIC = 0.195 µg/mL). The cytotoxicity results demonstrated that at a concentration of 1 mg/mL, LNAO has potent breast cancer (MCF-7), and hepatocellular carcinoma (Hep 3B) cancer cells inhibitory activities of 98% and 95%, respectively. Importantly, we are the first to show that LNAO significantly hinders hepatocellular carcinoma spheroids’ formation capacity in a 3D model. These results show that LNAO is a promising natural source with powerful antioxidant, antidiabetic, anticancer, and antimicrobial activities that could be exploited in the future to treat a variety of diseases.

In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (Ia-Ic and IIa-IId) underwent characterization via HRMS, 1H-, 13CAPT-NMR, and MicroED. Their efficacy against α-amylase was assessed in vitro, while MTS assays were employed to gauge cytotoxicity across cancer and normal cell lines. Additionally, the antidiabetic impact of compound IIc was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, IIa and IIc displayed potent α-amylase inhibition (IC50 values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC50 > 150 µM), suggesting their safety. Compound IId demonstrated significant activity against four cancer cell lines (26–65 µM). In vivo experiments revealed that five doses of IIc substantially reduced mice blood glucose levels from 252.2 mg/dL to 173.8 mg/dL in contrast to the control group. The compelling in vitro anticancer efficacy of IIc and its safety for normal cells underscores the need for further in vivo assessment of this promising compound. This research highlights the potential of benzodioxol derivatives as candidates for the future development of synthetic antidiabetic drugs.