High-throughput sequencing reveals the structure and metabolic resilience of desert microbiome confronting climate change.

Introduction: Desert ecosystems harbor a unique microbial diversity that is crucial for ecological stability and biogeochemical cycles. An in-depth understanding of the biodiversity, compositions, and functions of these microbial communities is imperative to navigate global changes and confront potential threats and opportunities applicable to agricultural ecosystems amid climate change. Methods: This study explores microbial communities in the rhizosphere and endosphere of desert plants native to the Arabian Peninsula using next-generation sequencing of the 16S rRNA gene (V3-V4 hypervariable region). Results: Our results reveal that each microbial community has a diverse and unique microbial composition. Based on alpha and beta diversity indices, the rhizosphere microbiome is significantly diverse and richer in microbial taxa compared to the endosphere. The data reveals a shift towards fast-growing microbes with active metabolism, involvement in nutrient cycling, nitrogen fixation, and defense pathways. Our data reveals the presence of habitat-specific microbial communities in the desert, highlighting their remarkable resilience and adaptability to extreme environmental conditions. Notably, we observed the existence of radiation-resistant microbes such as Deinococcus radiotolerans, Kocuria sp., and Rubrobacter radiotolerans which can tolerate high levels of ionizing radiation. Additionally, examples of microbes exhibiting tolerance to challenging conditions include Nocardioides halotolerans, thriving in high-salinity environments, and hyperthermophilic microbes such as Quasibacillus thermotolerans. Moreover, functional analysis reveals enrichment in chaperon biosynthesis pathways associated with correct protein folding under heat stress conditions. Discussion: Our research sheds light on the unique diversity of desert microbes and underscores their potential applications to increase the resilience of agriculture ecosystems, offering a promising strategy to fortify crops against the challenges posed by climate change, ultimately supporting sustainable food production for our ever-expanding global population.

Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity.

BACKGROUND: The World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has killed millions of people and had a terrible effect on society. The transmembrane protease serine 2 (TMPRSS2) enzyme is essential in the initial phases of the interplay between the SARSCoV-2 and the host cells by assisting viral entrance. METHODS: This observational case-control study involved 150 participants, 100 adult patients with COVID-19, 50 of whom appeared healthy and had no history of or symptoms of COVID-19 infection when the study was conducted. Between January and April 2022, patients were taken as inpatients in isolation units or through recruitment from the COVID-19 clinic at Kasr Al-Ainy Cairo University Hospitals. According to the National Institutes of Health guidelines (2021), they were categorised into three categories: mild, moderate, and severe. TMPRSS2 p.(Val197Met) variant genotyping was evaluated using TaqMan Real-Time PCR. RESULTS: The study showed a substantial difference between the mild and severe COVID-19 patient groups regarding their TMPRSS2 (p.Val197Met) genotypes (P value = 0.046). The C allele was significantly more prevalent in the mild, moderate and severe COVID-19 patient categories (77.8%, 89.7% and 91.7%, respectively) and the control group (80%). Meanwhile, the T allele was more prevalent in the mild (22.2%) and control (20%) groups. There was a statistically significant difference in allelic distribution between the mild and severe groups (P value = 0.034). CONCLUSION: The study showed a connection between the TMPRSS2 gene variant p.(Val197Met) and the degree of illness. We concluded that the T(mutant) allele was protective against severe COVID-19 because it was linked to lesser disease severity.

Perspectives on Corrosion Inhibition Features of Novel Synthesized Gemini-Fluorinated Cationic Surfactants Bearing Varied Spacers for Acid Pickling of X60-Steel: Practical, and In Silico Calculations.

Through our present study, three novel Gemini-fluorinated cationic surfactants bearing different spacers (FSG6-2, FSG6-4, and FSG6-6) were synthesized, and their structures were explained via different spectroscopic instruments such as 1H, 13C, and 19F NMR spectra. The surface activity of the as-prepared surfactants was examined. The inhibiting influence of FSG6 molecules on the X60 steel corrosion in the pickling solution (HCl) was examined by diverse methods comprising electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and X-ray photoelectron spectroscopy (XPS) experimentations, and computational calculations. The inhibition effectiveness of FSG6 surfactants followed the order of 93.37% (FSG6-2) < 96.74% (FSG6-4) < 98.37% (FSG6-6) at 2.0 × 10-4 M. The FSG6 surfactants function as mixed-type inhibitors, according to PDP investigations. The H2O molecules that adsorbed on the steel interface were substituted with surfactant molecules, and the surfactant's inhibitory activity is likely caused by the improvement in an adsorptive layer on the steel substrate, as specified by the EIS results. The Langmuir isotherm describes the absorption of FSG6 molecules on the metal surface. The XPS investigations validate the steel interface's extremely protective nature. The mechanism of interaction between FSG6 molecules with an X60-steel employing the DFT calculations and MC simulations methods was also examined and discussed.

Prognostic Value of Plasma miR-29a Evaluation in Chronic Lymphocytic Leukemia Patients.

OBJECTIVE: Dysregulation of microRNA expression could attenuate the course of chronic lymphocytic leukemia (CLL). Therefore, the aim of our study is to address the association between miR-29a expression and other prognostic markers in CLL patients. METHODS: miR-29a expression was determined by quantitative real-time PCR in the plasma of 158 CLL patients at diagnosis beside 21 healthy controls in a prospective study. RESULTS: The levels of miR-29a expression were found to be significantly higher in CLL patients as compared to healthy controls (P<0.001). Moreover, a significant association between high miR-29a expression and poor prognostic markers (high expression of CD38 and ZAP70, high LDH levels, Stage III Rai stage, unfavorable cytogenetic finding, time to first treatment (TTFT) and patients outcome (P<0.001 for All). Using ROC curve, we have reported that miR-29a expression levels (29a<0.76 vs >0.76) is able to discriminate severity subgroups of CLL patients. CONCLUSION: Up regulation of miR-29a expression at CLL diagnosis was detected. Determination of miR-29a expression concentration levels at diagnosis could be demonstrated as a prognostic biomarker in CLL patients.

Prognostic Value of Serum CD200 Concentrations in Chronic Lymphocytic Leukemia.

BACKGROUND: little is known regarding the prognostic value of soluble CD200 (sCD200)in  chronic lymphocytic leukemia patients. Therefore, the objective of our study is  to address the prognostic value of sCD200 antigen concentration on  CLL patients outcome. METHODS: Determination of  serum sCD200 was done using ELISA kit in 158 CLL patients at diagnosis  before start of therapy beside 21 healthy controls. RESULTS: sCD200 concentration levels was significantly higher in CLL patients as compared to healthy controls.  High sCD200 was associated with poor prognostic markers (high expression of CD38+% and ZAP70+, high LDH, high risk Rai stages, unfavorable cytogenetic finding, time to first treatment (TTT) as well as patients outcome (P<0.001 for All). sCD200 at cut-off value ( 752.5 pg/ml) could predicts TTT with specificity 83.4%. CONCLUSION: Determination of sCD200 concentration levels at diagnosis could be used as a prognostic biomarker in CLL patients.

Novel Imine-Tethering Cationic Surfactants: Synthesis, Surface Activity, and Investigation of the Corrosion Mitigation Impact on Carbon Steel in Acidic Chloride Medium via Various Techniques.

Novel imine-tethering cationic surfactants, namely (E)-3-((2-chlorobenzylidene)amino)-N-(2-(decyloxy)-2-oxoethyl)-N,N-dimethylpropan-1-aminium chloride (ICS-10) and (E)-3-((2-chlorobenzylidene)amino)-N,N-dimethyl-N-(2-oxo-2-(tetradecyloxy)ethyl)propan-1-aminium chloride (ICS-14), were synthesized, and the chemical structures were elucidated by various spectroscopic approaches. The surface properties of the target-prepared imine-tethering cationic surfactants were investigated. The effects of both synthesized imine surfactants on carbon steel corrosion in a 1.0 M HCl solution were investigated by weight loss (WL), potentiodynamic polarization (PDP), and scanning electron microscopy (SEM) methods. The outcomes show that the inhibition effectiveness rises with raising the concentration and diminishes with raising the temperature. The inhibition efficiency of 91.53 and 94.58 % were attained in the presence of the optimum concentration of 0.5 mM of ICS-10 and ICS-14, respectively. The activation energy (Ea) and heat of adsorption (Qads) were calculated and explained. Additionally, the synthesized compounds were investigated using density functional theory (DFT). Monte Carlo (MC) simulation was utilized to understand the mechanism of adsorption of inhibitors on the Fe (110) surface.

Synthesis, Characterization, and Docking Study of Novel Thioureidophosphonate-Incorporated Silver Nanocomposites as Potent Antibacterial Agents.

Newly synthesized mono- and bis-thioureidophosphonate (MTP and BTP) analogues in eco-friendly conditions were employed as reducing/capping cores for 100, 500, and 1000 mg L-1 of silver nitrate. The physicochemical properties of silver nanocomposites (MTP(BTP)/Ag NCs) were fully elucidated using spectroscopic and microscopic tools. The antibacterial activity of the nanocomposites was screened against six multidrug-resistant pathogenic strains, comparable to ampicillin and ciprofloxacin commercial drugs. The antibacterial performance of BTP was more substantial than MTP, notably with the best minimum inhibitory concentration (MIC) of 0.0781 mg/mL towards Bacillus subtilis, Salmonella typhi, and Pseudomonas aeruginosa. Among all, BTP provided the clearest zone of inhibition (ZOI) of 35 ± 1.00 mm against Salmonella typhi. After the dispersion of silver nanoparticles (AgNPs), MTP/Ag NCs offered dose-dependently distinct advantages over the same nanoparticle with BTP; a more noteworthy decline by 4098 × MIC to 0.1525 × 10-3 mg/mL was recorded for MTP/Ag-1000 against Pseudomonas aeruginosa over BTP/Ag-1000. Towards methicillin-resistant Staphylococcus aureus (MRSA), the as-prepared MTP(BTP)/Ag-1000 displayed superior bactericidal ability in 8 h. Because of the anionic surface of MTP(BTP)/Ag-1000, they could effectively resist MRSA (ATCC-43300) attachment, achieving higher antifouling rates of 42.2 and 34.4% at most optimum dose (5 mg/mL), respectively. The tunable surface work function between MTP and AgNPs promoted the antibiofilm activity of MTP/Ag-1000 by 1.7 fold over BTP/Ag-1000. Lastly, the molecular docking studies affirmed the eminent binding affinity of BTP over MTP-besides the improved binding energy of MTP/Ag NC by 37.8%-towards B. subtilis-2FQT protein. Overall, this study indicates the immense potential of TP/Ag NCs as promising nanoscale antibacterial candidates.

Prognostic value of MTSS1 gene expression on acute leukemia patients outcome.

Background: This study aimed to evaluate the prognostic value of the MTSS1 gene expression in patients with acute leukemia. Patients & methods: MTSS1 gene expression was quantified in 120 newly diagnosed acute leukemia patients, by quantitative reverse transcription PCR at diagnosis and after induction chemotherapy therapy. Results: Baseline MTSS1 gene expression was significantly higher in acute leukemia patients compared to the control group (p < 0.001). Acute leukemia patients with low baseline MTSS1 gene expression at diagnosis have significantly shorter overall survival and disease-free survival compared with those with higher expression (p < 0.001 for both). Conclusion: Downregulation of MTSS1 gene expression at diagnosis was associated with poor outcome in either cytogenetic acute myeloid leukemia or B-cell acute lymphoblastic leukemia.

Facile synthesis, larvicidal activity, biological effects, and molecular docking of sulfonamide-incorporating quaternary ammonium iodides as acetylcholinesterase inhibitors against Culex pipiens L.

Insecticides participate with a vital role in our lives especially in preventing the spread of human diseases via controlling the dangerous pests. It is a challenge to identify alternatives to the ordinary insecticides with new mode of action to be used for mosquitoes' control in an environmentally sustainable manner. Using a facile two-step procedure, three novel series of sulfonamide-incorporating quaternary ammonium iodides (3a-i, 4a-i and 5a-i) were synthesized and their chemical structures were successfully characterized. The uncharged sulfonamide intermediates (2a-i) were constructed through simple amidation of the corresponding (hetero)aryl sulfonyl chlorides then the cationic target molecules were formed by quaternizing the tertiary nitrogen with methyl, ethyl, and allyl iodides. The larvicidal activities and biological effects of most synthesized compounds against Culex pipiens L. were extensively investigated and they exhibited good and comparable activities to temephos. Among these hybrids, 4a showed the most potent activity with LC50 = 26.71 ppm. Additionally, the developmental durations of larval and pupal stages were significantly prolonged after treatment with all concentrations of 4h. At high concentration (160 ppm) of 4a and 4b, no adults emerged due to the complete death of pupae, and consequently zero growth index. Moreover, the results of the molecular docking demonstrated that the activities of compounds correlate partially to their binding with acetylcholinesterase (AChE) and it is not the sole parameter for determining the activity.

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) Polymorphisms in Adult Patients with Acute B-cell Lymphoblastic Leukemia.

BACKGROUNDS: Neutropenia after intensive chemotherapy of acute lymphoblastic leukemia (ALL) could lead to infectious complications that affect outcome of acute leukemia patients. Many single-nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) can affect the genetic susceptibility to infections. We investigated the impact of different SNPs on the incidence of developing sepsis and pneumonia in patients with newly diagnosed B-ALL following induction chemotherapy. SUBJECTS AND METHODS: We analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly& Thr399Ile) genes using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) in a case control study of 40 precursor B-ALL patients and 50 control subjects. The risk of developing sepsis and pneumonia were assessed by multiple logistic regression analyses. RESULTS: The presence of the TLR-2 AG polymorphism was significantly associated with pneumonia in B-ALL patients. Furthermore, TLR4 Thr399Ile AG was a risk factor for sepsis in B-ALL patients. Moreover; Significant association between TLR-2 AA, TLR-4 CC and TL-4 AA genotypes and longer OS were detected in studied B-ALL patients. CONCLUSION: We concluded that TLR-4 (AG and CT) genotypes are associated with high susceptibility to sepsis and pneumonia respectively; while, TLR-2, TLR-4 AA and TLR-4 CC genotypes  could predict good B-ALL patients outcome.

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI. METHODS: In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice. RESULTS: Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment. CONCLUSIONS: All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

The assessment of the protective impact of spidroin extract against UV-A radiation damage by using earthworms (Aporrectodea caliginosa) as a robust human skin model via macroscopic and histological observations.

Numerous studies have confirmed the damage caused by excessive exposure to ultraviolet-A rays. Malignant melanoma and skin cancer are two of the most serious health consequences. Thus, the UV-A protectant is intended to protect the skin, especially the two primary layers of skin (epidermis that represents the interface between the body and its surroundings and dermis). Spider silk is the most powerful natural fibre due to its regeneration, biocompatibility, antimicrobial, wound healing, antiseptic, and blood clotting properties. This work targeted to determine the protective effect of spidroin extract against UV-A radiation damage. Earthworms Aporrectodea caliginosa were collected from Assiut University's farm. Each set of ten earthworms was separated into six groups and placed in a plastic container. Webs of spiders collected from trees and old houses. Spidroin was extracted and utilised in this work to determine the potential effects of topical application on UV-A protection. The experiment is divided into two sections: (1) UV-A exposure and (2) the use of spidroin extract to protect the earthworms from ultraviolet radiation. Two control groups (1،2) of worms were not received UV-A exposure, and four groups (3,4,5,6) were exposed to UVR-A. In contrast, groups (5,6) were received spidroin extract before exposure to UV-A. Each group from the groups (3,4,5,6) was exposed for three consecutive days (» hour/day, ½ hour/day, and 1 h/day), using a UV-Lamp with a wavelength of 366 nm. The histopathological changes revealed that after 1/4 h of UV exposure, the cuticle was swollen with a slightly detached epithelium. The cuticle was down after 1/2 h of exposure, and the epidermis was totally damaged and necrosed. After 1 h, the exposure showed destruction of the epidermis in the circular muscle with a loss of muscle filament integrity, varying size, and altered nucleus form, along with mild disintegration of longitudinal muscle. Spidroin extract is critical for earthworm protection against UV-A radiation damage and able to regeneration. For the first time, morphological and histological analysis was established to detect the Spidroin extract evaluated for topical application on earthworms. Earthworms can be considered as a robust human skin model prior to UV-A exposure. It induces a complete protective effect against UV-A radiation damage in earthworms.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Fluorinated Candidates as PI3K Inhibitors: Targeting Fluorophilic Binding Sites.

Highly fluorinated candidates containing anticancer pharmacophores like thiosemicarbazone (5a-e) and its cyclic analogues hydrazineylidenethiazolidine (6a-e), 2-aminothiadiazole (7a-e), and 2-hydrazineylidenethiazolidin-4-one (8a-e) were synthesized, and their cytotoxic activity was assayed against 60 tumor cell lines. Compounds 6c, 7b, and 8b displayed the most potent activity with lower toxic effects on MCF-10a. In vitro phosphatidylinositol 3-kinase (PI3K) enzyme inhibition was performed. Compound 6c displayed half-maximal inhibitory concentration (IC50, µM) values of 5.8, 2.3, and 7.9; compound 7b displayed IC50 values of 19.4, 30.7, and 73.7; and compound 8b displayed IC50 values of 77.5, 53.5, and 121.3 for PI3Kα, ß, and δ, respectively. Moreover, cell cycle progression caused cell cycle arrest at the S phase for compounds 6c and 8b and at G1/S for compound 7b, while apoptosis was induced. In silico studies; molecular docking; physicochemical parameters; and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis were performed. The results showed that compound 6c is the most potent one with a selectivity index (SI) of 39 and is considered as a latent lead for further optimization of anticancer agents.

Predictive Value of miR-146a rs2431697 Polymorphism to Myelofibrosis Progression in Patients with Myeloproliferative Neoplasm.

BACKGROUND: Bone marrow myelofibrosis (BMF) that develop on top of Polycythaemia vera (PV) and essential thrombocythemia leads to shortening of the patient's overall survival. This study aimed to address the impact of miR-146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression. PATIENTS AND METHODS: The study included 88 myeloproliferative neoplasm (40 PV; 27 ET; 21 MF) and 90 healthy controls. For all investigated subjects miR-146a rs2431697 genotypes were identified by sequencing and the expression of miR-146a; IL-1ß; NF-κB; a NOD-like receptor family, pyrin domain containing 3 (NLRP3) (NLRP3) genes were estimated by real time PCR. RESULTS: miR146a genotypes revealed that there was significant association between TT and TC genotypes with MF. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1ß; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients' group. Multivariate analysis identified TT genotype as poor predictor of MF progression. CONCLUSION: miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1ß; NF-κB; NLRP3 genes might help  in hindering of  MF progression in  MPN patients,
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Construction, petro-collecting/dispersing capacities, antimicrobial activity, and molecular docking study of new cationic surfactant-sulfonamide conjugates.

Surfactants with their diverse activities have been recently involved in controlling the spread of new coronavirus (COVID-19) pandemic as they are capable of disrupting the membrane surrounding the virus. Using hybrids approach, we constructed a novel series of cationic surfactant-sulfonamide conjugates (3a-g) through quaternization of the as-prepared sulfonamide derivatives (2a-g) with n-hexadecyl iodide followed by structural characterization by spectroscopy (IR and NMR). Being collective properties required in petroleum-processing environment, the petro-collecting/dispersing capacities on the surface of waters with different degrees of mineralization, and the antimicrobial performance against microbes and sulfate-reducing bacteria (SRB) that mitigate microbiological corrosion were investigated for the synthesized conjugates. Among these conjugates, 3g (2.5% aq. solution) exhibited the strongest ability to disperse the thin petroleum film on the seawater surface, whereas KD is 95.33% after 96 h. In diluted form, 3f collected the petroleum layer on distilled water surface (Kmax = 32.01) for duration exceeds 4 days. Additionally, almost all compounds revealed high potency and comparable action with standard antimicrobials, especially 3b and 3f, which emphasize their role as potential biocides. Regarding biocidal activity against SRB, 3g causes a significant reduction in the bacterial count from 2.8 × 106 cells/mL to Nil. Moreover, the conducted molecular docking study confirms the strong correlation between RNA polymerase binding with bioactivity against microbes over other studied proteins (threonine synthase and cyclooxygenase-2).

Therapeutic Impact of ODN2088 to Block TLR9 Activity in Induced Liver Fibrosis Mice.

BACKGROUND AND OBJECTIVE: Liver fibrosis is the result of an excessive accumulation of extracellular matrix that develops when inflammation and chronic injury form scar tissue in the liver. Toll-like receptor 9 (TLR9) plays a central role in the innate immune response by recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). This study aimed to show the therapeutic effects of TLR9 antagonist oligonucleotide (ODN) 2088 on liver fibrogenesis. MATERIALS AND METHODS: Mice were injected intraperitoneally with carbon tetrachloride (CCl4) or corn oil twice weekly for up to 8 weeks. Mice were also injected with CpG ODN 2088 (50 µg/20 g) daily for the last 4 weeks. At sacrifice, the serum level of liver enzyme activity was measured. Expression of pro-inflammatory and pro-fibrotic biomarkers was analyzed in liver tissue. RESULTS: TLR9 antagonist, CpG ODN 2088, remarkably decreased the haptic inflammation and fibrosis during CCl4 administration. Treatment with CpG ODN 2088 resulted in reduced serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). That was paralleled with inhibition in the production of intrahepatic inflammatory and fibrotic factors including collagen, α-Smooth Muscle Actin (SMA), Transforming Growth Factor-beta (TGF-ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α). Proliferation (Ki-67) and apoptosis (caspase-3) markers were highly suppressed after CpG ODN 2088 administration. CONCLUSION: Our results indicate that TLR9 antagonist, ODN 2088, showed protective effects against hepatics inflammation and fibrosis in the CCl4-induced fibrosis model. These observations suggest that ODN 2088 can be a potential therapeutic target for liver fibrosis treatment.

Structure-based design, synthesis, and biological evaluation of novel piperine-resveratrol hybrids as antiproliferative agents targeting SIRT-2.

A series of novel piperine-resveratrol hybrids 5a-h was designed, synthesized, and structurally elucidated by IR, and 1H, 13C, and 19F NMR. Antiproliferative activities of 5a-h were evaluated by NCI against sixty cancer cell lines. Compound 5b, possessing resveratrol pharmacophoric phenolic moieties, showed a complete cell death against leukemia HL-60 (TB) and Breast cancer MDA-MB-468 with growth inhibition percentage of -0.49 and -2.83, respectively. In addition, 5b recorded significant activity against the other cancer cell lines with growth inhibition percentage between 80 to 95. New 5a-h hybrids were evaluated for their inhibitory activities against Sirt-1 and Sirt-2 as molecular targets for their antiproliferative action. Results showed that compounds 5a-h were more potent inhibitors of Sirt-2 than Sirt-1 at 5 µm and 50 µm. Compound 5b showed the strongest inhibition of Sirt-2 (78 ± 3% and 26 ± 3% inhibition at 50 µM and 5 µM, respectively). Investigation of intermolecular interaction via Hirschfeld surface analysis indicates that these close contacts are mainly ascribed to the O-H⋯O hydrogen bonding. To get insights into the Sirt-2 inhibitory mechanism, a docking study was performed where 5b was found to fit nicely inside both extended C-pocket and selectivity pocket and could compete with the substrate acyl-Lys. Another possible binding pattern showed that 5b could act by partial occlusion of the NAD+ C-pocket. Collectively, these findings would contribute significantly to better understanding the Sirt-2 inhibitory mechanism in order to develop a new generation of refined and selective Sirt-2 inhibitors.

Modulation of cell cycle progression and chromatin dynamic as tolerance mechanisms to salinity and drought stress in maize.

Salinity and drought are the major abiotic stresses that disturb several aspects of maize plants growth at the cellular level, one of these aspects is cell cycle machinery. In our study, we dissected the molecular alterations and downstream effectors of salinity and drought stress on cell cycle regulation and chromatin remodeling. Effects of salinity and drought stress were determined on maize seedlings using 200 mM NaCl (induced salinity stress), and 250 mM mannitol (induced drought stress) treatments, then cell cycle progression and chromatin remodeling dynamics were investigated. Seedlings displayed severe growth defects, including inhibition of root growth. Interestingly, stress treatments induced cell cycle arrest in S-phase with extensive depletion of cyclins B1 and A1. Further investigation of gene expression profiles of cell cycle regulators showed the downregulation of the CDKA, CDKB, CYCA, and CYCB. These results reveal the direct link between salinity and drought stress and cell cycle deregulation leading to a low cell proliferation rate. Moreover, abiotic stress alters chromatin remodeling dynamic in a way that directs the cell cycle arrest. We observed low DNA methylation patterns accompanied by dynamic histone modifications that favor chromatin decondensation. Also, the high expression of DNA topoisomerase 2, 6 family was detected as consequence of DNA damage. In conclusion, in response to salinity and drought stress, maize seedlings exhibit modulation of cell cycle progression, resulting in the cell cycle arrest through chromatin remodeling.

Corrosion Control of Carbon Steel in Water-Based Mud by Nanosized Metallo-Cationic Surfactant Complexes During Drilling Operations.

In this work, three nanometal complexes named cetyltrimethyammonium dibromodichloro zincate (CT-Zn), cetyltrimethyammonium dibromodichloro cuprate (CT-Cu), and cetyltrimethyammonium dibromodichloro manganesate (CT-Mn) were prepared, characterized, and evaluated as corrosion inhibitors for carbon steel in water-based mud (WBM). The chemical structure of the prepared complexes was confirmed by the use of Fourier transform infrared spectroscopy, Raman spectroscopy, elemental analysis, atomic absorption spectroscopy, dynamic light scattering, and thermogravimetric analysis techniques. The surface tension of the complexes was measured. The critical micelle concentrations and some of the surface properties were also determined. The compounds were evaluated as corrosion inhibitors for carbon steel in the prepared WBM using potentiodynamic polarization and weight loss methods during the static and dynamic conditions of the drilling operations. The results indicated that the prepared metal complexes showed high anticorrosion action as the inhibition efficiency increased gradually with the increase in the concentrations of the prepared complexes until it reached the maximum value (93.1%) at 300 ppm for CT-Cu. The order of inhibition efficiency of these inhibitors was as follows: CT-Cu > CT-Zn > CT-Mn. The polarization curves showed that these complexes acted as mixed-type inhibitors. According to the results, the adsorption of these compounds obeyed Langmuir adsorption isotherm. Surface analysis of the carbon steel samples was investigated using scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. Rheological properties, gel strength, thixotropy, and filtration properties were also measured according to American Petroleum Institute specifications.