Synthesis, Anticancer Activity, and Molecular Docking of New 1,2,3-Triazole Linked Tetrahydrocurcumin Derivatives.

Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring mono-alkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds 4g and 4k, showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound 4g exhibited anticancer activity with a IC50 value of 1.09 ± 0.17 µM against human colon carcinoma HCT-116 and 45.16 ± 0.92 µM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound 4g can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which 4g exerts its anti-colon cancer effect may be through inhabiting the binding of APC-Asef. Compound 4g can be used as a promising lead for further exploration of potential anticancer agents.

Strong association between sarcopenic obesity and non-alcoholic fatty liver disease: An observational study with ISarcoPRM algorithm.

BACKGROUND: In recent times, sarcopenia and non-alcoholic fatty liver disease (NAFLD) have garnered widespread attention in public health. Nevertheless, the relationship between sarcopenia and NAFLD remains uncertain. This study investigated the association between NAFLD and sarcopenia in the elderly population. METHODS: In this cross-sectional study, 1099 adults aged 60 and older participated. The participants were classified based on their body composition, and the International Society of Physical and Rehabilitation Medicine's diagnostic algorithm (ISarcoPRM) was utilized to diagnose sarcopenia, while the fatty liver index was utilized to diagnose NAFLD. Binary logistic regression analysis determined the correlation between NAFLD and sarcopenia. RESULTS: Of the 1099 participants, 213 (58.2 %) males and 480 (65.5 %) females were afflicted with NAFLD. After adjusting for other clinical factors, exercise was found to decrease the likelihood of NAFLD in females (but not in males) by approximately 70 % [relative risk (RR): 0.312, 95 % confidence interval (CI): 0.182-0.547]. In addition, sarcopenia was not discerned as a risk factor for NAFLD in either gender (both p > 0.05). However, obesity increased the likelihood of NAFLD in males by 27.5 (95 % CI: 10.4-73.1) and in females by 28.1 (95 % CI: 17.1-46.4), and sarcopenic obesity increased the likelihood of NAFLD by 49.5 (95 % CI: 11.1-219.1) in males and 35.5 (95 % CI: 18.5-68.2) in females (all p < 0.001). CONCLUSION: Our study suggests that sarcopenia is not a risk factor for NAFLD in non-obese elderly subjects. However, a strong association was observed between obesity, especially sarcopenic obesity, and NAFLD. Regular physical activity seems protective for NAFLD in older females.

Red Sea Sponge Callyspongia siphonella Extract Induced Growth Inhibition and Apoptosis in Breast MCF-7 and Hepatic HepG-2 Cancer Cell Lines in 2D and 3D Cell Cultures.

Introduction: The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge Callyspongia siphonella (C. siphonella) on HepG-2 and MCF-7 cancer cell lines. Methods: C. siphonella was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays. Results: Fifteen compounds were identified in the C. siphonella extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC50 values of 35.6 ± 6.9 µg/mL and 64.4 ± 8 µg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC50 values of 5.1 ± 2 µg/mL for MCF-7 and 166.4 ± 27 µg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres. Discussion and Conclusion: The anticancer activity is attributed to the bioactive compounds. The C. siphonella extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.

Discovery of new 1,3-diphenylurea appended aryl pyridine derivatives as apoptosis inducers through c-MET and VEGFR-2 inhibition: design, synthesis, in vivo and in silico studies.

Interest has been generated in VEGFR-2 and c-MET as potential receptors for the treatment of different malignancies. Using aryl pyridine derivatives with 1,3-diphenylurea attached, a number of promising dual VEGFR-2 and c-MET inhibitors were developed and synthesized. Regarding the molecular target, compounds 2d, 2f, 2j, 2k, and 2n had potent IC50 values of 65, 24, 150, 170, and 18 nM against c-MET, respectively. Additionally, they had potent IC50 values of 310, 35, 290, 320, and 24 nM against VEGFR-2, respectively. Regarding cytotoxicity, compounds 2d, 2f, 2j, 2k and 2n exhibited potent cytotoxicity against MCF-7 with IC50 values in the range 0.76-21.5 µM, and they showed promising cytotoxic activity against PC-3 with IC50 values in the range 1.85-3.42 µM compared to cabozantinib (IC50 = 1.06 µM against MCF-7 and 2.01 µM against PC-3). Regarding cell death, compound 2n caused cell death in MCF-7 cells by 87.34-fold; it induced total apoptosis by 33.19% (8.04% for late apoptosis, 25.15% for early apoptosis), stopping their growth in the G2/M phase, affecting the expression of apoptosis-related genes P53, Bax, caspases 3 and 9 and the anti-apoptotic gene, Bcl-2. In vivo study illustrated the anticancer activity of compound 2n by reduction of tumor mass and volume, and the tumor inhibition ratio reached 56.1% with an improvement of hematological parameters. Accordingly, compound 2n can be further developed as a selective target-oriented chemotherapeutic against breast cancer.

Selective adhesion of nitrogen-containing toxic gasses on hexagonal boron phosphide monolayer: a computational study.

CONTEXT: Various toxic gasses are being released into the environment with the increasing industrialization. However, detecting these gasses at low concentrations has become one of the main challenges in environmental monitoring and protection. Thus, developing sensors with high performance to detect toxic gasses is of utmost significance. For this purpose, researchers have introduced 2D materials thanks to their unique electronic qualities and large specific surface area. Within this piece of research, a hexagonal boron phosphide monolayer (h-BPML) is employed as the substrate material. The adhesion behavior of ambient nitrogen-containing toxic gasses, i.e., N2O, NH3, NO2, and NO, onto the h-BPML is investigated through DFT computations. The adhesion energy values for gasses NO and NO2 were calculated to be - 0.509 and - 0.694 eV on the h-BPML, respectively. Meanwhile, the absorbed energy values for gasses NH3 and N2O were found to be - 0.326 and - 0.119 eV, respectively. The recovery time, DOS, workfunction, and Bader charges were computed based on four optimal adhesion structures. After the absorption of NO on the h-BPML, the value of workfunction of a monolayer decreased from 1.54 to 0.47 eV. This amount of decrease was the greatest among the other gasses absorbed. By comparing the investigated parameters, it can be concluded that the h-BPML has a greater tendency to interact with NO gas compared to other gasses, and it can be proposed as a sensor for NO gas. METHOD: Within this piece of research, the sensitivity of the h-BPML to four nitrogenous toxic gasses, namely, N2O, NH3, NO2, and NO, was investigated using the DFT with HSE06 hybrid functional by using GAMESS software. For this purpose, we computed the DOS, workfunction, and the Bader charges for the four adhesion systems with most stability.

Parsonage Turner syndrome after needle electromyography: a needle in a haystack.

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Characteristics and outcomes of urinary tract infections caused by Enterococci: A multicenter retrospective study from two tertiary hospitals in Saudi Arabia.

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. Very few studies have investigated the characteristics of enterococcal infections. We aimed to characterize patients with urinary tract infections (UTIs) due to Enterococci and their outcomes. This was a retrospective cohort study between June 2012-November 2022. Patients who had clinically and microbiologically confirmed Enterococcal UTI based on a urine culture positive for E. faecalis or E. faecium with a count of ≥105 CFU/mL and having urinary tract symptoms were included. A total of 396 patients were eligible and included. The patients had a median age of 61 years and were mostly females (56.8 %). The most common characteristics were hospitalization in a non-ICU ward, having a urinary catheter, and recent use of antibiotics within the last 3 months (66.4 %, 59.3 %, and 51.8 %, respectively). Infection with E. faecalis was more common than E. faecium (77.3 % vs. 22.7 %). However, the latter exhibited higher rates of antibiotic resistance (P < 0.001 to several antibiotics) and was associated with significantly higher median C-reactive protein level (26.7 vs. 13 mg/dL; P = 0.025), mortality (23 % vs. 10.1 %; P = 0.002), and median length of stay (25 vs. 11.5 days; P < 0.001). We found that most patients with enterococcal UTIs had a history of having a urinary catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. E. faecium-infected patients experienced more severe episodes and poorer outcomes compared to patients infected with E. faecalis; thus, would need more aggressive therapy.

Ziziphus spina-christi L. extract attenuates bleomycin-induced lung fibrosis in mice via regulating TGF-ß1/SMAD pathway: LC-MS/MS Metabolic profiling, chemical composition, and histology studies.

Ancient Egyptians (including Bedouins and Nubians) have long utilized Ziziphus spina-christi (L.), a traditional Arabian medicinal herb, to alleviate swellings and inflammatory disorders. It is also mentioned in Christian and Muslim traditions. Ziziphus spina-christi L. (Family: Rhamnaceae) is a plentiful source of polyphenols, revealing free radical scavenging, antioxidant, metal chelating, cytotoxic, and anti-inflammatory activities. Herein, different classes of the existing bioactive metabolites in Z. spina-christi L. were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. The study also aimed to assess the anti-inflammatory and antifibrotic properties of Z. spina-christi L. extract against bleomycin-induced lung fibrosis in an experimental mouse model. 32 male Swiss Albino mice were assigned into 4 groups; the first and second were the normal control group and the bleomycin positive control (single 2.5 U/kg bleomycin intratracheal dose). The third and fourth groups received 100 and 200 mg/kg/day Z. spina-christi L. extract orally for 3 weeks, 2 weeks before bleomycin, and 1 week after. The bioactive metabolites in Z. spina-christi L. extract were identified as phenolic acids, catechins, flavonoids, chalcones, stilbenes, triterpenoid acids, saponins, and sterols. The contents of total phenolic compounds and flavonoids were found to be 196.62 mg GAE/gm and 33.29 mg QE/gm, respectively. In the experimental study, histopathological examination revealed that lung fibrosis was attenuated in both Z. spina-christi L.- treated groups. Z. spina-christi L. extract downregulated the expression of nuclear factor kappa B (NF-κB) p65 and decreased levels of the inflammatory markers tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and c-Jun N-terminal kinase (JNK) in lung tissue. Z. spina-christi L. also downregulated the expression of the fibrotic parameters collagen-1, alpha-smooth muscle actin (α-SMA), transforming growth factor-beta 1 (TGF-ß1), matrix metalloproteinase-9 (MMP-9) and SMAD3, with upregulation of the antifibrotic SMAD7 in lung tissue. Overall, the present study suggests a potential protective effect of Z. spina-christi L. extract against bleomycin-induced lung fibrosis through regulation of the TGF-ß1/SMAD pathway.

Functional and financial analysis of an inclined step solar desalination using phase change nanomaterials.

Recent decades have seen a shortage of water, which has led scientists to concentrate on solar desalination technologies. The present study examines the solar water desalination system with inclined steps, while considering various phase change materials (PCMs). The findings suggest that the incorporation of PCM generally enhances the productivity of the solar desalination system. Additionally, the combination of nanoparticles has been used to PCM, which is a popular technique utilized nowadays to improve the efficiency of these systems. The current investigation involves the transient modeling of a solar water desalination system, utilizing energy conservation equations. The equations were solved using the Runge-Kutta technique of the ODE23s order. The temperatures of the salt water, the absorbent plate of the glass cover, and the PCM were calculated at each time. Without a phase changer, the rate at which fresh water is produced is around 5.15 kg/m2·h. The corresponding mass flow rates of paraffin, n-PCM I, n-PCM III, n-PCM II, and stearic acid are 22.9, 28.9, 5.9, 11.9, and 73 kg/m2·h. PCMs, with the exception of stearic acid, exhibit similar energy efficiency up to an ambient temperature of around 29°. However, at temperatures over 29°, n-PCM II outperforms other PCM.

Deciphering morphology patterns of environmental microfibers: Insights into source apportionment.

Microfibers, a prevalent form of microplastics, undergo diverse environmental interactions resulting in varied morphological changes. These changes can offer insights into their environmental trajectories. Despite its importance, comprehensive studies on microfiber morphology are scarce. This study collected 233 microfibers from the East China Sea and South China Sea. Based on morphological features observed in microscopic images of microfibers, such as curvature, cross-sectional shapes, diameter variations, and crack shapes, we identified a general morphological pattern, classifying the environmental microfibers into three distinct morphological types. Our findings highlight noticeable differences in morphological metrics (e.g., length, diameter, and surface roughness) across three types, especially the diameter. Microfibers of Type I had an average diameter of 19.45 ± 4.93 µm, significantly smaller than Type II (263.00 ± 75.15 µm) and Type III (299.68 ± 85.62 µm). Within the three-dimensional (3D) space fully defined by these quantitative parameters, the clustering results of microfibers are also consistent with the proposed morphology pattern, with each category showing a potential correlation with specific chemical compositions. Type I microfibers correspond to synthetic cellulose, while 94.79 % of Types II and III are composed of polymers. Notably, we also validated the great applicability of the morphology categories to microfibers in diverse environmental compartments, including water and sediments in nearshore and offshore areas. This classification aids in the efficient determination of microfiber sources and the assessment of their ecological risks, marking a significant advancement in microfiber environmental studies.

A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre.

OBJECTIVE: To assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DESIGN: Retrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. SETTING/PARTICIPANTS: High-volume non-surgical regional Australian tertiary referral centre. MAIN OUTCOME MEASUREMENTS: Index & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. RESULTS: From 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/- 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. CONCLUSIONS: Advances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).