A comparative study of the biosynthesis of CuNPs by Niallia circulans G9 and Paenibacillus sp. S4c strains: characterization and application as antimicrobial agents.

BACKGROUND: Biosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents. RESULTS: This investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs' SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13-100 nm by the G9 strain and spherical nanoparticles with a size range of 5-40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883. CONCLUSION: The present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.

Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

Efficacy of artemether against toxocariasis in mice: parasitological and immunopathological changes in brain, liver, and lung.

Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15th dpi (early treatment), and at the 35th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.

Identification of novel sulfathiazole-triazolo-chalcone hybrids as VEGFR-2/EGFR dual inhibitors with antiangiogenic activity and apoptotic induction.

Certain sulfathiazole-triazolo chalcone hybrids were identified as anticancer agents with dual vascular endothelial growth factor receptor-2 (VEGFR-2)/epidermal growth factor receptor (EGFR) kinase inhibitory effect. All of the compounds were evaluated for their cytotoxic activity against the MCF-7 and HepG-2 tumor cell lines. Compounds 11g, 11h, and 11j exhibited the most potent antiproliferative activity against both cancer cell lines, with good safety toward WI-38 normal cells. Thus, they were further assessed for VEGFR-2 inhibitory activity. They have suppressed VEGFR-2 enzyme at IC50 of 0.316, 0.076, and 0.189 µM, respectively in comparison to sorafenib (IC50 = 0.035 µM). EGFR enzyme inhibition was further screened for the most potent inhibitors, 11h and 11j, where they displayed enhanced potency with IC50 of 0.085 and 0.108 µM, respectively, compared to erlotinib (IC50 = 0.037 µM). Compounds 11h and 11j were additionally investigated for inhibition of comparable kinases, PDGFR-ß and B-Raf, where results assessed adequate selectivity of both compounds toward the VEGFR-2 and EGFR kinases. Furthermore, the wound healing assay of compound 11h manifested a percent wound closure of 65.18% in MCF-7 cells compared to doxorubicin (58.51%) and untreated cells (97.77%), proving its antiangiogenic activity. The cell cycle assay of MCF-7 cells treated with 11h demonstrated cell cycle arrest at the S phase. Moreover, compound 11h induced apoptosis with a 44-fold increase compared to that induced in the control MCF-7 cells. Molecular docking results of compounds 11h and 11j established their efficacies, and in silico studies showed convenient safety profiles with drug-likeness properties.

Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice.

There are currently insufficient anthelmintic medications available for the treatment of toxocariasis. For instance, Albendazole (ABZ) is the preferred medication, but its effectiveness against tissue-dwelling parasites is limited. In addition, Metformin (MTF) is a widely used oral antidiabetic medication that is considered to be safe for treatment. This study aimed to investigate any potential effects of MTF, alone or in combination with ABZ, on mice infections caused by Toxocara canis (T. canis). The efficacy of the treatment was assessed in the acute and chronic phases of the infection by larval recovery and histopathological, immunohistochemical, and biochemical studies. The results showed that combined therapy significantly reduced larval counts in the liver, brain, and muscles and ameliorated hepatic and brain pathology. It reduced oxidative stress and TGF-ß mRNA expression and increased FGF21 levels in the liver. It decreased TNF-α levels and MMP-9 expression in the brain. In addition, it increased serum levels of IL-12 and IFN-γ and decreased serum levels of IL-4 and IL-10. In the acute and chronic phases of the infection, the combined treatment was more effective than ABZ alone. In conclusion, this study highlights the potential role of MTF as an adjuvant in the treatment of experimental T. canis infection when administered with ABZ.

Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study.

Spirochromanes incorporating Schiff's bases and semicarbazones 4a-e and 5a-j were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds 5a, 5b and 5g possessed the highest antiproliferative activity among the tested compounds,with an IC50 range of 1.154-9.09 µM. Compound 5j selectively inhibited the PC3 cell proliferation (IC50 = 5.47 µM). Spirochromanes 5a, 5b and 5g exhibited high inhibitory activity against EGFR (IC50 = 0.116, 0.132, and 0.077 µM, respectively) and HER2 (IC50 = 0.055, 0.210 and 0.085 µM, respectively) compared with the references, erlotinib (IC50 = 0.090 and 0.038 µM, respectively) and gefitinib (IC50 = 0.052 and 0.072 µM, respectively). Cell cycle analysis and apoptosis results showed that compounds 5a, 5b and 5g arrested growth inthe S phase, and the programmed cell death induced by these compounds was an apoptotic mechanism rather than a necrotic pathway. Molecular docking studies of spirochromanes 5a, 5b and 5g to EGFR and HER2 binding sites were performed to explore the orientation mode and interaction.

The impact of ß-glucan on the therapeutic outcome of experimental Trichinella spiralis infection.

Trichinellosis is a cosmopolitan zoonosis that is caused mainly by Trichinella spiralis infection. The human disease ranges from mild to severe and fatality may occur. The treatment of trichinellosis still presents a challenge for physicians. Anti-inflammatory drugs are usually added to antiparasitic agents to alleviate untoward immuno-inflammatory responses and possible tissue damage but they are not without adverse effects. Thus, there is a need for the discovery of safe and effective compounds with anti-inflammatory properties. This study aimed to evaluate the activity of ß-glucan during enteral and muscular phases of experimental T. spiralis infection as well as its therapeutic potential as an adjuvant to albendazole in treating trichinellosis. For this aim, mice were infected with T. spiralis and divided into the following groups: early and late ß-glucan treatment, albendazole treatment, and combined treatment groups. Infected mice were subjected to assessment of parasite burden, immunological markers, and histopathological changes in the small intestines and muscles. Immunohistochemical evaluation of NF-κB expression in small intestinal and muscle tissues was carried out in order to investigate the mechanism of action of ß-glucan. Interestingly, ß-glucan potentiated the efficacy of albendazole as noted by the significant reduction of counts of muscle larvae. The inflammatory responses in the small intestine and skeletal muscles were mitigated with some characteristic qualitative changes. ß-glucan also increased the expression of NF-κB in tissues which may account for some of its effects. In conclusion, ß-glucan showed a multifaceted beneficial impact on the therapeutic outcome of Trichinella infection and can be regarded as a promising adjuvant in the treatment of trichinellosis.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights.

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

Parasitic infections as potential risk factors for attention deficit hyperactivity disorder (ADHD) in children.

Attention deficit hyperactivity disorder (ADHD) represents a mysterious neuropsychiatric alarming concern due to indefinite etiopathogenesis among children. Notably, the studies which investigated the correlation between ADHD and parasitic infections are insufficient. Therefore, this research aimed to assess the correlation between ADHD and some tissue dwelling and intestinal parasitic infections in children. The study was conducted on 200 children, including 100 children suffering from ADHD (Group I) and 100 healthy children as a control group (Group II). All caregivers fulfilled predesigned sociodemographic form and Conners parent rating scale (CPRS-48) questionnaire. Blood samples were collected to determine hemoglobin level as well as relative eosinophilic count. The presence of anti-Toxoplasma IgG and anti-Toxocara IgG in serum by Enzyme-Linked Immunosorbent Assay (ELISA) was further investigated. Also, micronutrients as zinc, iron, and copper levels were measured. Schistosoma antigen was investigated in urine samples. Stool samples were subjected to direct wet smear, concentration technique and modified Ziehl-Neelsen (MZN) staining for coccidian parasites detection. Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica antigens were investigated in stool samples. Group I expressed more liability to sociodemographic risk factors, decreased levels of Hb, iron, zinc, and copper with statistically significant difference (P < 0.001). Comparison between Group I and Group II regarding the detected parasitic infections exhibited statistically significant difference except Schistosoma antigen positivity which expressed no statistical significance. The present study concluded that the parasitic infections with their consequences are potential risk factors in children with ADHD indicating that their early diagnosis and treatment may help in ADHD prevention.

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (4a-d), 1,3,4-thiadiazoles (6a-d), and pyrimidines (8a-d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.

Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies.

Multi-target inhibitors represent useful anticancer agents with superior therapeutic attributes. Here in, two novel series of benzimidazole-triazole hybrids were designed, synthesised as multi-target EGFR, VEGFR-2 and Topo II inhibitors, and evaluated for anticancer activity. Compounds 5a and 6g were the most potent analogues against four cancer cell lines, HepG-2, HCT-116, MCF-7 and HeLa, and were further evaluated for EGFR, VEGFR-2, and Topo II inhibition. Compound 5a was especially good inhibitor for EGFR (IC50 = 0.086 µM) compared to Gefitinib (IC50 = 0.052 µM), moderate VEGFR-2 inhibitor (IC50 = 0.107 µM) compared to Sorafenib (IC50 = 0.0482 µM), and stronger Topo II inhibitor (IC50 = 2.52 µM) than Doxorubicin (IC50 = 3.62 µM). Compound 6g exhibited moderate EGFR and VEGFR-2 inhibition and weaker Topo II inhibition. DNA binding assay, cell cycle analysis, apoptotic induction, molecular docking, and physicochemical studies were additionally implemented to explore the plausible mechanism of the active compounds.

Microbial evasion of the complement system: a continuous and evolving story.

The complement system is a fundamental part of the innate immune system that plays a key role in the battle of the human body against invading pathogens. Through its three pathways, represented by the classical, alternative, and lectin pathways, the complement system forms a tightly regulated network of soluble proteins, membrane-expressed receptors, and regulators with versatile protective and killing mechanisms. However, ingenious pathogens have developed strategies over the years to protect themselves from this complex part of the immune system. This review briefly discusses the sequence of the complement activation pathways. Then, we present a comprehensive updated overview of how the major four pathogenic groups, namely, bacteria, viruses, fungi, and parasites, control, modulate, and block the complement attacks at different steps of the complement cascade. We shed more light on the ability of those pathogens to deploy more than one mechanism to tackle the complement system in their path to establish infection within the human host.

Maximization of red pigment production from Streptomyces sp. LS1 structure elucidation and application as antimicrobial/antifouling against human pathogens and marine microbes.

BACKGROUND: Natural dyes are present in living organisms such as animals and plants and microorganisms such as fungi, bacteria, algae, and yeast. Pigments are fast and easy growth by using cheap components and do not effect by environmental conditions because they required some physical factors like heat, light, and pH and also they have many biotechnological applications such as medical and industrial needs. The natural pigments can act as antimicrobial agents and are used in drug manufacturing. Also, it can be used in the food industry as natural colorants instead of the synthetic colorants due to their safety on human health and low toxicity when emitted into the environment. RESULTS: A pigmented actinomycetes LS1 strain isolated from El Mahmoudia canal (sediment soil) located in Egypt was microscopically examined and identified as Streptomyces sp. by molecular approach. Extraction, purification, and characterization of produced red pigment metabolite like carotenoids related were established based on spectroscopic studies and comparing the data from the literature. Factors (nutritional and physical) influencing red pigmentation by this isolate were investigated through One Variable At Time (OVAT), and then, the optimal levels of the significant key variables were recorded. Also, the productivity yield reached 30 mg of dried purified pigment/gram dry weight. The biological activity of the red product was tested against Gram-positive and Gram-negative marine bacterial pathogens; the recorded antimicrobial activity is more prominent against (P. aeruginosa ATCC 9027, K. pneumoniae ATCC 13883, S. aureus ATCC 6538, B. subtilis ATCC 6633 and E. coli ATCC 10418) at nearly 0.07 mg mL-1 concentration. Also, the tested red pigment showed a positive antifouling activity (AF) against marine microbes; the activity increased by increasing the pigment concentrations from 1 to 3 mg mL-1. CONCLUSION: The present work focused on the optimization of culture conditions for the production of red pigment by Streptomyces sp. LS1; then, the antibacterial activity and antifouling activity of the produced pigments were tested.

Production and statistical optimization of cholesterol-oxidase generated by Streptomyces sp. AN strain.

BACKGROUND: Cholesterol oxidases (CHOs) have attracted enormous attention because of their wide biotechnological potential. The present study explores the production of CHOs by Streptomyces sp. AN. Evaluation of culture conditions affecting enzyme production, medium optimization and released metabolite characteristics were also investigated. RESULTS: The current work reports the isolation of 37 colonies (bacteria/actinobacteria) with different morphotypes from different soil/water samples. The isolate-coded AN was selected for its high potency for CHO production. Morphological characteristics and the obtained partial sequence of 16srRNA of AN showed 99.38% identity to Streptomyces sp. strain P12-37. Factors affecting CHO production were evaluated using Plackett-Burman (PB) and Box-Behnken (BB) statistical designs to find out the optimum level of the most effective variables, namely, pH, starch, NH4NO3 and FeSO4.7H2O with a predicted activity of 6.56 U/mL. According to this optimization, the following medium composition was considered to be optimum (g/L): cholesterol 1, starch 6, MgSO4.7H2O 0.1, CaCl2 0.01, FeSO4.7H2O 0.1, NH4NO3 23.97, yeast extract (YE) 0.2, K2HPO4 0.01, KH2PO4 0.1, NaCl 0.01, Tween 20 0.01, pH 6.36 and incubation temperature (30 °C) for 9 days. Spectophotometric analysis for released metabolites against cholesterol (standard) via Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) was carried out. FTIR spectrum showed the appearance of new absorption peaks at 1644 and 1725cm-1; this confirmed the presence of the Keto group (C=O) stretch bond. Besides, fermentation caused changes in thermal properties such as melting temperature peak (99.26; 148.77 °C), heat flow (- 8; - 3.6 Mw/mg), capacity (- 924.69; - 209.77 mJ) and heat enthalpy (- 385.29; 69.83 J/g) by comparison to the standard cholesterol as recognized through DSC thermogram. These changes are attributed to the action of the CHO enzyme and the release of keto derivatives of cholesterol with different properties. CONCLUSION: Streptomyces sp. AN was endowed with the capability to produce CHO. Enzyme maximization was followed using a statistical experimental approach, leading to a 2.6-fold increase in the overall activity compared to the basal condition. CHO catalyzed the oxidation of cholesterol; this was verified by the appearance of a new keto group (C=O) peak at 1644 and 1725 cm-1 observed by FTIR spectroscopic analysis. Also, DSC thermogram demonstrates the alteration of cholesterol triggered by CHO.

Synthesis, antitumor, and apoptosis-inducing activities of novel 5-arylidenethiazolidine-2,4-dione derivatives: Histone deacetylases inhibitory activity and molecular docking study.

The antitumor activity of the newly synthesized 5-arylidenethiazolidine-2,4-dione derivatives 18a-f and 19a-f was investigated, compared to doxorubicin (IC50 = 4.17-8.87 µM) and SAHA (IC50 = 2.70-7.11 µM). Among the tested molecules, compounds 18b, 18c, 18f, 19d, and 19e displayed the highest antitumor activity against cancer cell lines (IC50 = 3.16-28.94 µM). Further, compounds 18b, 18c, 18f, and 19d were tested as Histone deacetylases (HDACs) inhibitors compared with Entinostat (IC50 = 0.093-0.75 µM). Compounds 18b, 18c, 18f, and 19d inhibited HDAC1, HDAC2, HDAC8, and HDAC6 enzymes with IC50 values ranging from 0.144 to 1.741 µM. In addition, compound 18b caused apoptosis via a mitochondrial-mediated pathway and led to cell cycle arrest at the G1 phase. It also increased caspases-3 and caspases-7 by 5.2-3.9 and 9.1-3.7 folds, respectively. The molecular docking analysis of compounds 18b and 18c revealed that they could bind to the active sites of HDAC1, HDAC2, HDAC8, and HDAC6 like co-crystallized inhibitors.

The beneficial metabolic actions of prolactin.

The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 µg/L) and very low (<7 µg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.

Novel diaryl ether derivatives as InhA inhibitors: Design, synthesis and antimycobacterial activity.

A new series of triclosan (TCL)-mimicking diaryl ether derivatives 7-25 were synthesized and evaluated as inhibitors of enoyl acyl carrier protein reductase InhA enzyme. In addition, these derivatives were screened as inhibitors of drug-susceptible (DS), multidrug-resistant (MDR), and extensive drug-resistant (XDR) Mycobacterium tuberculosis (MTB) strains. Most compounds exihibted superior anti-TB activities and improved ClogP compared to TCL as a standard drug. The present work has led to the identification of compounds 14, 19 and 24 which possess remarkable activities against DS, MDR and XDR MTB strains with MIC values of 1.95, 3.9 and 15.63 µg/ml, respectively for compound 14, 1.95, 3.9 and 7.81 µg/ml, respectively for compound 19 and 0.98, 1.95 and 3.9 µg/ml, respectively for compound 24. Most compounds did not exhibit toxicity to HePG2 normal cell line. Compounds 14, 19 and 24, presenting the best MIC values, were further evaluated as inhibitors of InhA enzyme. They showed high binding affinities in the micromolar range with IC50 values of 1.33, 0.6, and 0.29 µM for compounds 14, 19, and 24, respectively. Furthermore, molecular docking approach was utilized to understand the difference in bioactivities between the new compounds. In particular, the results revealed strong binding interactions and high docking scores of compounds 14, 19 and 24, which could correlate with their high activities. Mainly, the molecular modelling study of compound 24 provides an excellent platform for understanding the molecular mechanism regarding InhA inhibition. Thus, compound 24 could be a lead compound for future development of new antitubercular drugs.

Examining Healthcare Professionals' Telehealth Usability before and during COVID-19 in Saudi Arabia: A Cross-Sectional Study.

COVID-19 has placed substantial stress on healthcare providers in Saudi Arabia as they struggle to avoid contracting the virus, provide continued care for their patients, and protect their own families at home from possible exposure. The demand for care has increased due to the need to treat COVID-19. This pandemic has created a surge in the need for care in select healthcare delivery specialties, forcing other nonurgent or elective care to halt or transition to telehealth. This study provides a timely description of how COVID-19 affected employment, telehealth usage, and interprofessional collaboration. The STROBE checklist was used. We developed a cross-sectional online survey design that is rooted and grounded in the Technology Acceptance Model (TAM). The TAM model allows us to identify characteristics that affect the use of telehealth technologies. The survey was deployed in November 2021 to local healthcare providers in Saudi Arabia. There were 66 individuals in the final sample. Both interprofessional satisfaction on frequency and quality were positively correlated with the frequency of interactions. The odds for satisfaction of frequency and quality were about 12 times (OR = 12.27) and 8 times 110 (OR = 8.24) more, respectively, for the participants with more than three times of interaction than the participants with no interaction at all. We also found that change in telehealth usage during the pandemic was positively associated with the Telehealth Usability Questionnaire (TUQ) scores. The estimated score for the participants who reported an increase in telehealth usage was 5.37, while the scores were lower for the participants reporting 'no change' and 'decreased usage'. Additional training on telehealth use and integration to improve interprofessionalism is needed.

Design and Synthesis of Benzene Homologues Tethered with 1,2,4-Triazole and 1,3,4-Thiadiazole Motifs Revealing Dual MCF-7/HepG2 Cytotoxic Activity with Prominent Selectivity via Histone Demethylase LSD1 Inhibitory Effect.

In this study, an efficient multistep synthesis of novel aromatic tricyclic hybrids incorporating different biological active moieties, such as 1,3,4-thiadiazole and 1,2,4-triazole, was reported. These target scaffolds are characterized by having terminal lipophilic or hydrophilic parts, and their structures are confirmed by different spectroscopic methods. Further, the cytotoxic activities of the newly synthesized compounds were evaluated using in vitro MTT cytotoxicity screening assay against three different cell lines, including HepG-2, MCF-7, and HCT-116, compared with the reference drug Taxol. The results showed variable performance against cancer cell lines, exhibiting MCF-7 and HepG-2 selectivities by active analogs. Among these derivatives, 1,2,4-triazoles 11 and 13 and 1,3,4-thiadiazole 18 were found to be the most potent compounds against MCF-7 and HepG-2 cancer cells. Moreover, structure-activity relationship (SAR) studies led to the identification of some potent LSD1 inhibitors. The tested compounds showed good LSD1 inhibitory activities, with an IC50 range of 0.04-1.5 µM. Compounds 27, 23, and 22 were found to be the most active analogs with IC50 values of 0.046, 0.065, and 0.074 µM, respectively. In addition, they exhibited prominent selectivity against a MAO target with apparent cancer cell apoptosis, resulting in DNA fragmentation. This research provides some new aromatic-centered 1,2,4-triazole-3-thione and 1,3,4-thiadiazole analogs as highly effective anticancer agents with good LSD1 target selectivity.

Histological Evaluation of Restylane Lyft Used as a Scaffold for Dental Pulp Regeneration in Non-Infected Immature Teeth in Dogs.

Commercially available hyaluronic acid dermal fillers used as a scaffold in regenerative endodontic procedures (REPs) have demonstrated attractive potentials. This study aimed to histologically evaluate the outcome of REPs using Restylane Lyft (HA) as a scaffold. REPs were performed on pulpless, immature roots in dogs (n = 69). The roots were divided into four groups: blood clot (BC), Restylane Lyft (BC + HA), negative control, and positive control. At 13 weeks postoperatively, hard tissue formation, vascularization, the presence of vascularized soft connective tissue and collagen fibers, the degree of inflammation within pulp spaces and/or periapical tissues, and apical closure were evaluated histologically. The vascularization and formation of loosely arranged collagen fibers within the regenerated soft connective tissues were observed significantly more in the BC+HA group (85% and 40%, respectively; p < 0.05) compared to the BC group (54.6% and 9.1%, respectively; p < 0.05). The degree of inflammation was significantly higher in the HA group than in the BC group; moderate to severe inflammatory cell infiltration was seen in 45% and 13.6% of the cases, respectively. The results of the present study suggest that Restylane Lyft combined with a blood clot used as a scaffold may improve the outcomes of REPs in non-infected, pulpless, immature teeth in dogs.