Evaluation status of current and emerging minimally invasive robotic surgical platforms.

BACKGROUND: The rapid adoption of robotics within minimally invasive surgical specialties has also seen an explosion of new technology including multi- and single port, natural orifice transluminal endoscopic surgery (NOTES), endoluminal and "on-demand" platforms. This review aims to evaluate the validation status of current and emerging MIS robotic platforms, using the IDEAL Framework. METHODS: A scoping review exploring robotic minimally invasive surgical devices, technology and systems in use or being developed was performed, including general surgery, gynaecology, urology and cardiothoracics. Systems operating purely outside the abdomen or thorax and endoluminal or natural orifice platforms were excluded. PubMed, Google Scholar, journal reports and information from the public domain were collected. Each company was approached via email for a virtual interview to discover more about the systems and to quality check data. The IDEAL Framework is an internationally accepted tool to evaluate novel surgical technology, consisting of four stages: idea, development/exploration, assessment, and surveillance. An IDEAL stage, synonymous with validation status in this review, was assigned by reviewing the published literature. RESULTS: 21 companies with 23 different robotic platforms were identified for data collection, 13 with national and/or international regulatory approval. Of the 17 multiport systems, 1 is fully evaluated at stage 4, 2 are stage 3, 6 stage 2b, 2 at stage 2a, 2 stage 1, and 4 at the pre-IDEAL stage 0. Of the 6 single-port systems none have been fully evaluated with 1 at stage 3, 3 at stage 1 and 2 at stage 0. CONCLUSIONS: The majority of existing robotic platforms are currently at the preclinical to developmental and exploratory stage of evaluation. Using the IDEAL framework will ensure that emerging robotic platforms are fully evaluated with long-term data, to inform the surgical workforce and ensure patient safety.

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.

Unraveling the impact of digital transformation on green innovation through microdata and machine learning.

How to use digitalization to support the green transformation of organizations has drawn much attention based on the rapid development of digitalization. However, digital transformation (DT) may be hindered by the "IT productivity paradox." Exploring the influence of DT on green innovation, we analyze panel data encompassing A-share listed companies in Shanghai and Shenzhen spanning the period from 2010 to 2018. It tests the DT's non-linear impact, employing a random-forest and mediation effect models. The results reveal that (i) DT can promote green innovation; (ii) regarding heterogeneity, the promotion effect is mainly manifested in enterprises in non-state-owned and highly competitive industries; (iii) based on mechanism testing, DT relies on two routes to encourage green innovation: improving environmental information disclosure and reducing environmental uncertainty; and (iv) random-forest analysis shows that DT exhibits an inverted U-shaped non-linear effect on green innovation, including the "IT productivity paradox." This study enhances the existing discourse on DT and green innovation by furnishing empirical substantiation for the non-linear influence exerted by DT on green innovation. Furthermore, it imparts insights into the mechanisms and contextual limitations governing this association.

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.

Insights into pressure injury prevention: Assessing the knowledge, attitudes, and practices of Palestinian nursing students.

AIM: To assess the knowledge, attitudes, and practices of Palestinian nursing students towards pressure injury prevention. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted with 455 nursing students recruited from Arab American University-Palestine, employing a total population sample. Data collection forms include socio-demographic information, the Pressure Ulcer Knowledge Assessment Tool, Attitude towards Pressure Ulcer Prevention Instrument and Pressure Injury Preventive Practices scale. RESULTS: The study found that students had a mean knowledge score of 54% (14.04/26), a positive attitude score of 75.8% (39.42/52), and demonstrated a fair level of practice 75.3% (30.12/40). Significant differences were observed in the Knowledge, Attitude, and Practice total scores, linked to academic year, clinical experience, and the number of attended departments during clinical training (p < 0.001). Additionally, weak but significant positive relationships were found between practice and attitude scores (r = 0.303, p < 0.001), practice and knowledge score (r = 0.211, p < 0.001), and a moderate positive significant relationship between knowledge and attitude scores (r = 0.567, p < 0.001). CONCLUSION: The study revealed insufficient knowledge, positive attitudes, and somewhat unsafe practices among nursing students regarding pressure injury prevention. It highlights the need for specific revisions in the nursing curriculum. Improvements can be achieved through detailed coverage in classrooms and laboratories, integrating simulation methods. Additionally, ensuring that students gain adequate experiences in clinical units, with a specific emphasis on pressure injury prevention, is crucial for improving students' capability and contribute to better pressure injury management.

Molecular docking, drug-likeness and DFT study of some modified tetrahydrocurcumins as potential anticancer agents.

The present study utilized molecular docking and density functional theory (DFT) approaches, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties to investigate the binding interactions, reactivity, stability, and drug-likeness of curcumin (1), tetrahydrocurcumin (2), and tetrahydrocurcumin derivatives (3-6) as potential anti-cancer agents. MGL (Molecular Graphic Laboratory) and Discovery Studio Visualizer (DSV) software employed for docking studies. Pharmacokinetic and pharmacodynamic (ADME-Tox) analyses were conducted using SwissADME and pKCSM web servers. Total Electron Density (TED) measurements identified molecular adsorption sites, considering various factors, including quantum chemical characteristics, to assess compound effectiveness using DFT method implanted in the Gaussian software. The binding energy (Eb) from docking simulations was used to evaluate inhibitory potential. ADMET analysis suggested favorable oral bioavailability and pharmacokinetics for all studied substances, excluding compound 4. DFT and docking investigations highlighted compounds 1, 2, and 6 as optimal scaffolds for drug design based on in silico screening tests.

A molecularly imprinted electrochemical sensor for specific and ultrasensitive determination of an aminoglycoside drug: the role of copper ions in the determination.

Herein, a molecularly imprinted polymer (MIP) was fabricated for specific sensing of an aminoglycoside e.g. kanamycin (KANA). Carbon paste modified with a MIP specific to Cu2+-KANA was first introduced. Copper (Cu2+) as a metal ion was used as a signal tracer and an amplifier, producing a current response measured by differential pulse voltammetry (DPV). Introducing the aminoglycoside drug into the solution containing Cu2+ did not affect the current response of the NIP/CPE. Under the optimum conditions, the as-fabricated sensor exhibited an increase in the current response in the range of 0.55-550 nM with a good limit of detection (LOD, S/N = 3) of 161 pM. The sensor exhibited many advantages including high sensitivity and selectivity, good stability and reproducibility, and cost-effectiveness. Moreover, it was successfully applied for the determination of KANA in milk and honey samples with RSD % not more than 3.3%, suggesting the reliability of the as-designed sensor.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-ß-Lactamase Producing Clinical Strain of Escherichia coli ST 131.

Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum ß-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a-h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate's identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a-h) demonstrated the binding pocket residues involved in the active site of the ß-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the ß-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.

Antibiotics for preventing infection at the surgical site: Single dose vs. multiple doses.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates.

A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability. In addition, most conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate test. The most promising conjugates were the unsubstituted and 6-substituted fluoro- and chloro-derivatives of 2-(trifluoromethyl)quinoline linked to ibuprofen by a propyl chain. Their anti-inflammatory activity was evaluated against LPS-stimulated inflammatory reactions in RAW264.7 mouse macrophages. In this regard, it was found that most of the conjugates were able to significantly reduce the release and production of nitric oxide in the LPS-stimulated macrophages. The secretion and expression of the pro-inflammatory cytokines IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) were also significantly suppressed.

Design, synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is critically involved in cancer angiogenesis. Blocking of VEGFR-2 signaling pathway proved effective suppression of tumor growth. Accordingly, two series of new triazoloquinoxaline-based derivatives were designed and synthesized as VEGFR-2 inhibitors. All in vitro cytotoxic activities of the synthesized compounds were evaluated against two human cancer cell lines (MCF-7 and HepG2). To confirm the potential mechanism of cytotoxicity, enzymatic assays against VEGFR-2 were estimated for all the target compounds. The results of VEGFR-2 inhibitory activity and cytotoxicity were in high correlation. Compound 22a exhibited the highest cytotoxic effect with IC50 values of 6.2 and 4.9 µM against MCF-7 and HepG2, respectively, comparing to sorafenib (IC50 = 3.53 and 2.18 µM). Such derivative showed the best VEGFR-2 inhibitory activity with an IC50 value of 3.9 nM, which is very close to that of sorafenib (IC50 = 3.13 nM). Moreover, compounds 22b, 23b, and 23e exhibited strong cytotoxic activity with IC50 values ranging from 11.7 to 15.3 µM. Also, these compounds showed promising VEGFR-2 inhibition with IC50 values of 4.2, 5.7, and 4.7 nM, respectively. In silico docking, ADMET, and toxicity studies were carried out for the synthesized compounds. The results revealed that some compounds have a good binding mode against VEGFR-2 and a high level of drug-likeness.

Targeting VEGFR-2 by new quinoxaline derivatives: Design, synthesis, antiproliferative assay, apoptosis induction, and in silico studies.

Twelve new triazolo[4,3-a]quinoxaline-based compounds are reported as anticancer agents with potential effects against vascular endothelial growth factor receptor-2 (VEGFR-2), using sorafenib as a reference molecule. With sorafenib as the positive control, the antiproliferative effects of the synthesized compounds against MCF-7 and HepG2 cells, as well as their VEGFR-2-inhibitory activities, were assessed. The most powerful VEGFR-2 inhibitor was compound 14a, which had an IC50 value of 3.2 nM, which is very close to that of sorafenib (IC50 = 3.12 nM). Furthermore, compounds 14c and 15d showed potential inhibitory activity against VEGFR-2, with IC50 values of 4.8 and 5.4 nM, respectively. Compound 14a caused apoptosis in HepG2 cells and stopped the cell cycle at the G2/M phase. In HepG2 cells, it also increased the levels of the proteases caspase-3 and caspase-9, as well as the Bax/Bcl-2 ratio. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) and toxicity experiments revealed that the synthesized agents had acceptable drug-likeness.

Low-Dose Tacrolimus Promotes the Migration and Invasion and Nitric Oxide Production in the Human-Derived First Trimester Extravillous Trophoblast Cells In Vitro.

Placentation is one of the most important determinants for a successful pregnancy, and this is dependent on the process of trophoblast migration and invasion. Progesterone receptors (PGR) are critical effectors of progesterone (P4) signaling that is required for trophoblast migration and invasion conducive to a successful gestation. In immune complicated pregnancies, evidence has shown that abnormal placentation occurs because of aberrant expression of PGR. Therapeutic intervention with tacrolimus (FK506) was able to restore PGR expression and improve pregnancy outcomes in immune-complicated gestations; however, the exact mode of action of tacrolimus in assisting placentation is not clear. Here, we attempt to uncover the mode of action of tacrolimus by examining its effects on trophoblast invasion and migration in the human-derived extravillous trophoblast (EVT) cell line, the HTR-8/SVneo cells. Using a variety of functional assays, we demonstrated that low-dose tacrolimus (10 ng/mL) was sufficient to significantly (p < 0.001) stimulate the migration and invasion of the HTR-8/SVneo cells, inducing their cytosolic/nuclear progesterone receptor expression and activation, and modulating their Nitric Oxide (NO) production. Moreover, tacrolimus abrogated the suppressive effect of the NOS inhibitor Nω- Nitro-L-Arginine Methyl Ester (L-NAME) on these vital processes critically involved in the establishment of human pregnancy. Collectively, our data suggest an immune-independent mode of action of tacrolimus in positively influencing placentation in complicated gestations, at least in part, through promoting the migration and invasion of the first trimester extravillous trophoblast cells by modulating their NO production and activating their cytosolic/nuclear progesterone-receptors. To our knowledge, this is the first report to show that the mode of action of tacrolimus as a monotherapy for implantation failure is plausibly PGR-dependent.

A Novel Green Micellar HPLC-UV Method for the Estimation of Vandetanib in Pure Form, Human Urine, Human Plasma and Human Liver Microsomes Matrices with Application to Metabolic Stability Evaluation.

Vandetanib (Caprelsa®; VNB) is a prescription medicine that is used for the treatment of medullary thyroid cancer that has disrupted other body parts or that cannot be removed by surgery. It is considered a tyrosine kinase inhibitor (TKI). Fast, sensitive and validated HPLC-UV was established for VNB quantification in pure human biological fluids (urine and plasma) and human liver microsomes (HLMs). This analytical methodology was applied also to the metabolic stability assessment of VNB. This method was performed using a phenyl column (250 mm × 4.6 mm id, 5 µm particle size). A sodium dodecyl sulphate solution (0.05 M, pH 3.0 using 0.02 M orthophosphoric acid) containing 0.3% triethylamine and 10% n-butanol was used as a mobile phase and was pumped isocratically at a flow rate of 0.7 mL/min and at a 260 nm detection wavelength. The total elution time was 6 min with an injection volume of 20 µL. The linearity of the established methodology ranged from 30 to 500 ng/mL in pure form and 50 to 500 ng/mL (r2 ≥ 0.9994) in human biological fluids and HLMs. No significant interference from the matrix components was observed. The proposed methodology revealed the benefits of being green, reliable and economic.

Synthesis, Antimicrobial, Anti-Virulence and Anticancer Evaluation of New 5(4H)-Oxazolone-Based Sulfonamides.

Since the synthesis of prontosil the first prodrug shares their chemical moiety, sulfonamides exhibit diverse modes of actions to serve as antimicrobials, diuretics, antidiabetics, and other clinical applications. This inspiring chemical nucleus has promoted several research groups to investigate the synthesis of new members exploring new clinical applications. In this study, a novel series of 5(4H)-oxazolone-based-sulfonamides (OBS) 9a-k were synthesized, and their antibacterial and antifungal activities were evaluated against a wide range of Gram-positive and -negative bacteria and fungi. Most of the tested compounds exhibited promising antibacterial activity against both Gram-positive and -negative bacteria particularly OBS 9b and 9f. Meanwhile, compound 9h showed the most potent antifungal activity. Moreover, the OBS 9a, 9b, and 9f that inhibited the bacterial growth at the lowest concentrations were subjected to further evaluation for their anti-virulence activities against Pseudomonas aeruginosa and Staphylococcus aureus. Interestingly, the three tested compounds reduced the biofilm formation and diminished the production of virulence factors in both P. aeruginosa and S. aureus. Bacteria use a signaling system, quorum sensing (QS), to regulate their virulence. In this context, in silico study has been conducted to assess the ability of OBS to compete with the QS receptors. The tested OBS showed marked ability to bind and hinder QS receptors, indicating that anti-virulence activities of OBS could be due to blocking QS, the system that controls the bacterial virulence. Furthermore, anticancer activity has been further performed for such derivatives. The OBS compounds showed variable anti-tumor activities, specifically 9a, 9b, 9f and 9k, against different cancer lines. Conclusively, the OBS compounds can serve as antimicrobials, anti-virulence and anti-tumor agents.

Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (Piper betle L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes.

Piper betle L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for type 2 diabetes patients. In this study, compounds of P. betle were screened to investigate the inhibitory action of alpha-amylase and alpha-glucosidase against type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7-O-glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target proteins alpha-amylase and alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = -45.02 kcal mol-1 for alpha-amylase and -38.288 for alpha-glucosidase) compared with control inhibitor acarbose, which had binding affinities of -36.796 kcal mol-1 for alpha-amylase and -29.622 kcal mol-1 for alpha-glucosidase. The apigenin-7-O-glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors' native ligand. Based on ADMET analysis, this phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities and had no significant side effects, making them prospective drug candidates for type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.

Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.

The spread of the Dengue virus over the world, as well as multiple outbreaks of different serotypes, has resulted in a large number of deaths and a medical emergency, as no viable medications to treat Dengue virus patients have yet been found. In this paper, we provide an in silico virtual screening and molecular dynamics-based analysis to uncover efficient Dengue infection inhibitors. Based on a Google search and literature mining, a large phytochemical library was generated and employed as ligand molecules. In this investigation, the protein target NS2B/NS3 from Dengue was employed, and around 27 compounds were evaluated in a docking study. Phellodendroside (-63 kcal/mole), quercimeritrin (-59.5 kcal/mole), and quercetin-7-O-rutinoside (-54.1 kcal/mole) were chosen based on their binding free energy in MM-GBSA. The tested compounds generated numerous interactions at Lys74, Asn152, and Gln167 residues in the active regions of NS2B/NS3, which is needed for the protein's inhibition. As a result, the stable mode of docked complexes is defined by various descriptors from molecular dynamics simulations, such as RMSD, SASA, Rg, RMSF, and hydrogen bond. The pharmacological properties of the compounds were also investigated, and no toxicity was found in computational ADMET properties calculations. As a result, this computational analysis may aid fellow researchers in developing innovative Dengue virus inhibitors.

Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 µM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski's rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.