2-Thioxo-3,4-dihydropyrimidine and thiourea endowed with sulfonamide moieties as dual EGFRT790M and VEGFR-2 inhibitors: Design, synthesis, docking, and anticancer evaluations.

The effectiveness of a new series of thiopyrimidine and thiourea containing sulfonamides moieties was tested on HCT-116, MCF-7, HepG2, and A549. HepG2 cell line was the one that all the new derivatives affected the most. The greatest potent compounds against the four HepG2, HCT116, MCF-7, and A549 cell lines were 8f and 8g with IC50 = 4.13, 6.64, 5.74, 6.85 µM and 4.09, 4.36, 4.22, 7.25 µM correspondingly. Compound 8g exhibited higher activity than sorafenib against HCT116 and MCF-7 but exhibited lower activity against HepG2 and A549. Moreover, compounds 8f and 8g exhibited higher activities than erlotinib on HepG2, HCT116, and MCF-7 but demonstrated lower activity on A549. The most potent cytotoxic derivatives 6f, 6g, 8c, 8d, 8e, 8f, and 8g were examined on normal VERO cell lines. Our derivatives have low toxicity on VERO cells with IC50 values ranging from 32.05 to 53.15 µM. Additionally, all compounds were assessed for dual VEGFR-2 and EGFRT790M inhibition effects. Compounds 8f and 8g were the most potent derivatives inhibited VEGFR-2 at IC50 value of 0.88 and 0.90 µM, correspondingly. As well, derivatives 8f and 8g could inhibit EGFRT790M demonstrating strongest effects with IC50 = 0.32 and 0.33 µM sequentially. Additionally, the greatest active derivatives ADMET profile was evaluated in relationship with sorafenib and erlotinib as reference agents. The data attained from docking were greatly related to that achieved from the biological testing.

Prodrugs of PKC modulators show enhanced HIV latency reversal and an expanded therapeutic window.

AIDS is a pandemic disease caused by HIV that affects 37 million people worldwide. Current antiretroviral therapy slows disease progression but does not eliminate latently infected cells, which resupply active virus, thus necessitating lifelong treatment with associated compliance, cost, and chemoexposure issues. Latency-reversing agents (LRAs) activate these cells, allowing for their potential clearance, thus presenting a strategy to eradicate the infection. Protein kinase C (PKC) modulators-including prostratin, ingenol esters, bryostatin, and their analogs-are potent LRAs in various stages of development for several clinical indications. While LRAs are promising, a major challenge associated with their clinical use is sustaining therapeutically meaningful levels of the active agent while minimizing side effects. Here we describe a strategy to address this problem based on LRA prodrugs, designed for controllable release of the active LRA after a single injection. As intended, these prodrugs exhibit comparable or superior in vitro activity relative to the parent compounds. Selected compounds induced higher in vivo expression of CD69, an activation biomarker, and, by releasing free agent over time, significantly improved tolerability when compared to the parent LRAs. More generally, selected prodrugs of PKC modulators avoid the bolus toxicities of the parent drug and exhibit greater efficacy and expanded tolerability, thereby addressing a longstanding objective for many clinical applications.

Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays.

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4H-chromene-3-carboxylates 7a-g, 8, and 11a-e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, hCAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.

A novel spectrofluorimetric method based on a reaction with an azoisoxazoles-benzenesulfonamide derivative for determination of uranium (VI) ions in water samples.

Selective fluorometric detection and determination of uranium ions is provided here using a novel fluorescent reagent, namely (E)-4-([4-hydroxynaphthalen-1-yl]diazenyl)-N-(5-methyleisoxazol-3-yl) benzenesulfonamide (UVI reagent). The UVI reagent offers a selective fluorescence enhancement behaviour at emission wavelength = 557 nm. The parameters affecting fluorometric detection of uranium ions, such as the pH, solvent type, ligand concentration, interaction time, and interfering ions, were investigated and adjusted. The proposed UVI reagent can detect and determine uranium ions even at low concentrations, for which the obtained limit of detection was 0.1 ppm. Additionally, this proposed determination protocol was successfully used to detect, monitor, and determine uranium ions in actual water samples.

Polymeric Nanocomposites for Environmental and Industrial Applications.

Polymeric nanocomposites (PNC) have an outstanding potential for various applications as the integrated structure of the PNCs exhibits properties that none of its component materials individually possess. Moreover, it is possible to fabricate PNCs into desired shapes and sizes, which would enable controlling their properties, such as their surface area, magnetic behavior, optical properties, and catalytic activity. The low cost and light weight of PNCs have further contributed to their potential in various environmental and industrial applications. Stimuli-responsive nanocomposites are a subgroup of PNCs having a minimum of one promising chemical and physical property that may be controlled by or follow a stimulus response. Such outstanding properties and behaviors have extended the scope of application of these nanocomposites. The present review discusses the various methods of preparation available for PNCs, including in situ synthesis, solution mixing, melt blending, and electrospinning. In addition, various environmental and industrial applications of PNCs, including those in the fields of water treatment, electromagnetic shielding in aerospace applications, sensor devices, and food packaging, are outlined.

Design, synthesis, molecular docking, in silico ADMET profile and anticancer evaluations of sulfonamide endowed with hydrazone-coupled derivatives as VEGFR-2 inhibitors.

A new series of sulfonamide endowed with hydrazone coupled to dimethyl and/or diethyl malonates were prepared. Various sulfa drugs were diazotized and followed by coupling with active methylene of dimethyl and/or diethyl malonate to afford the new intermediates hydrazones 3a-c and 4a-c. The reactivity of hydrazone derivatives towards hydrazines was investigated. Thus, a novel series of 3,5-dioxopyrazolidine7a-cwere obtained by treatment with hydrazine hydrate. When hydrazones were allowed to react with phenyl hydrazine, the alkyl 2-((4-(N-(substituted)sulfamoyl)phenyl)diazenyl)-3-oxo-3-(2-phenylhydrazinyl)propanoateswere obtained 8a-c and/or 10a-c. Their anticancer activities were evaluated against HepG2, HCT-116 and MCF-7. HepG2 was the most sensitive one. In particular, compounds 7c, 7b and 10c were found to be the most potent derivatives with IC50 = 6.43 ± 0.5, 9.66 ± 0.8, 10.57 ± 0.9 µM, 8.65 ± 0.7, 7.49 ± 0.6, 14.29 ± 1.3 µM and 8.97 ± 0.7, 10.13 ± 0.9, 13.82 ± 1.1 µM respectively. Sorafenib and doxorubicin were used as reference drugs. The most potent derivatives 7a, 7b, 7c, 8c and 10c were tested for their cytotoxicity against normal VERO cell lines. Compounds 7a, 7b, 7c, 8c and 10c are respectively, 2.41, 4.85, 4.08, 3.23 and 5.89 fold times more toxic in HCT116 than in VERO normal cells. Moreover, the most active anti-proliferative derivatives 7a, 7b, 7c, 8c and 10c were subjected to further biological study to evaluate their inhibitory potentials against VEGFR-2. The tested compounds displayed high to good inhibitory activity with IC50 values ranging from 0.14 ± 0.02 to 0.23 ± 0.03 µM. Among them, compounds 7c, 7b and 10c were found to be the most potent derivative that inhibited VEGFR-2 at IC50 values of 0.14 ± 0.02, 0.15 ± 0.02 and 0.15 ± 0.02 µM respectively. sorafenib was used as reference drug. Furthermore, ADMET profile was evaluated for the four most active compounds in comparison to doxorubicin as a reference drug. The data obtained from docking studies were highly correlated with that obtained from the biological screening.

Distribution, abundance and natural enemies of the invasive tomato leafminer, Tuta absoluta (Meyrick) in Kenya.

Tuta absoluta (Meyrick) has become a serious menace to sustainable production of tomato in Kenya. A survey was conducted between April 2015 and June 2016 to determine its distribution, abundance, infestation, and damage levels on tomato, and associated natural enemies. Trap counts of T. absoluta moths were recorded in all surveyed 29 counties, which indicated its nationwide distribution irrespective of altitude. Tuta absoluta was present in both open fields and greenhouses. The highest moth/trap/day was 115.38 ± 15.90. Highest leaf infestation was 92.22% and the highest number of mines and larvae per leaf were 3.71 ± 0.28 and 2.16 ± 0.45, respectively. Trap captures in terms of moth/trap/day were linearly and positively related to leaf infestations in open fields (R2 = 0.81) and greenhouses (R2 = 0.61). Highest fruits' infestation and damage were 60.00 and 59.61%, respectively, while the highest number of mines per fruit was 7.50 ± 0.50. Nesidiocoris tenuis (Reuter) and Macrolophus pygmaeus (Rambur) were identified as predators of T. absoluta larvae. Nine species of larval parasitoids were recovered from infested foliage, with a combined parasitism of 7.26 ± 0.65%. Hockeria species was the most dominant (31.25%) and accounted for 12.88 ± 1.47% parasitism. Two species of larval parasitoids, Hockeria and Necremnus were obtained from sentinel plants with an average parasitism of 1.13 ± 0.25. The overall abundance and parasitism rates of recovered natural enemies were low to effectively control the field populations of T. absoluta. These findings form the basis of researching and developing effective and sustainable management strategies for the pest.

Concordances and correlations between anthropometric indices of obesity: a systematic review.

OBJECTIVES: The pandemic of overweight and obesity has become a major clinical and public health concern worldwide. Anthropometric indices are indirect and quantitative tools used to identify individuals at increased risk of body fat-related morbidity. The aim of this systematic review was to assess the concordances and correlations between anthropometric indices of obesity in adults and whether these indices can be used interchangeably. STUDY DESIGN: Systematic review. METHODS: A literature search was conducted in three databases of peer-reviewed publications (PubMed, Scopus, and Embase). Further, the first 10 pages of Google Scholar were also searched for relevant studies. RESULTS: There were strong correlations between body mass index (BMI) and waist circumference (WC) and between BMI and waist-to-height ratio (WHtR), and a weak correlation between BMI and neck circumference (NC). There was a very strong correlation between WC and WHtR and a moderate correlation between WC and NC. There were moderate concordances between BMI and WC and between BMI and WHtR and good concordance between WC and WHtR. CONCLUSION: BMI, WC, and WHtR indices can be moderately used interchangeably with caution. More studies in adult populations using statistical tests of concordance and adjusting for differences in ethnicity, age, gender, and weight quantiles are needed.

Phytochemical Profiling, In Vitro and In Silico Anti-Microbial and Anti-Cancer Activity Evaluations and Staph GyraseB and h-TOP-IIß Receptor-Docking Studies of Major Constituents of Zygophyllum coccineum L. Aqueous-Ethanolic Extract and Its Subsequent Fractions: An Approach to Validate Traditional Phytomedicinal Knowledge.

Zygophyllum coccineum, an edible halophytic plant, is part of the traditional medicine chest in the Mediterranean region for symptomatic relief of diabetes, hypertension, wound healing, burns, infections, and rheumatoid arthritis pain. The current study aimed to characterize Z. coccineum phytoconstituents, and the evaluations of the anti-microbial-biofilm, and anti-cancers bioactivities of the plant's mother liquor, i.e., aqueous-ethanolic extract, and its subsequent fractions. The in silico receptors interaction feasibility of Z. coccineum major constituents with Staph GyraseB, and human topoisomerase-IIß (h-TOP-IIß) were conducted to confirm the plant's anti-microbial and anti-cancer biological activities. Thirty-eight secondary metabolites of flavonoids, stilbene, phenolic acids, alkaloids, and coumarin classes identified by LC-ESI-TOF-MS spectrometric analysis, and tiliroside (kaempferol-3-O-(6''''-p-coumaroyl)-glucoside, 19.8%), zygophyloside-F (12.78%), zygophyloside-G (9.67%), and isorhamnetin-3-O-glucoside (4.75%) were identified as the major constituents. A superior biofilm obliteration activity established the minimum biofilm eradication concentration (MBEC) for the chloroform fraction at 3.9-15.63 µg/mL, as compared to the positive controls (15.63-31.25 µg/mL) against all the microbial strains that produced the biofilm under study, except the Aspergillus fumigatus. The aqueous-ethanolic extract showed cytotoxic effects with IC50 values at 3.47, 3.19, and 2.27 µg/mL against MCF-7, HCT-116, and HepG2 cell-lines, respectively, together with the inhibition of h-TOP-IIß with IC50 value at 45.05 ng/mL in comparison to its standard referral inhibitor (staurosporine, IC50, 135.33 ng/mL). This conclusively established the anti-cancer activity of the aqueous-ethanolic extract that also validated by in silico receptor-binding predicted energy levels and receptor-site docking feasibility of the major constituents of the plant's extract. The study helped to authenticate some of the traditional phytomedicinal properties of the anti-infectious nature of the plant.

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.

EFFICACY OF HEMOSTATIC AGENTS IN ENDODONTIC SURGERY: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: Adequate hemostasis is a critical step in endodontic surgery. It facilitates the procedure and affects the success and prognosis of the operation. This systematic review and network meta-analysis (NMA) aimed to systematically assess the efficacy of hemostatic agents in endodontic surgery and to identify the most effective ones. METHODS: PubMed, Scopus, Embase, Cochrane Library, Web of Science, ProQuest, and EBSCOhost databases were searched up to December 2020. We included randomized controlled trials (RCTs) evaluating the efficacy of different hemostatic measures in endodontic surgery, and their risk of bias was assessed using Cochrane's randomized trial tool (RoB 2.0). Frequentist network meta-analysis was conducted, with Odds Ratios and 95% confidence intervals (OR, 95% CI) as effect estimates using the "netmeta" package in R. The quality of evidence was assessed using the CINeMA approach. RESULTS: Six RCTs involving 353 patients (mean age 48.12 y) were included. NMA revealed that aluminum chloride achieved higher hemostatic efficacy than epinephrine (OR = 2.55, 95% CI [1.41, 4.64]), while there was non-significant difference when compared with PTFE strips + epinephrine (OR = 1.00, 95% CI [0.35, 2.90]), electrocauterization (OR = 2.67, 95% CI [0.84, 8.46]), or ferric sulfate (OR = 8.65, 95% CI [0.31, 240.92]). Of all hemostatic agents, aluminum chloride ranked first in control bleeding during endodontic surgery (P-score = 0.84), followed by PTFE strips + epinephrine (P-score = 0.80), electrocauterization (P-score = 0.34), epinephrine (P-score = 0.34), ferric sulfate (P-score = 0.18). The quality of evidence was very low. CONCLUSIONS: Based on the limited data, aluminum chloride provides better hemostasis than epinephrine, while there was no significant difference between the remaining hemostatic agents used in endodontic surgery, which could help clinicians choose the hemostatic agent that achieves adequate hemostasis. achieve adequate hemostasis. Given insufficient evidence, future RCTs addressing this evidence gap are required.

Design, green synthesis, molecular docking and anticancer evaluations of diazepam bearing sulfonamide moieties as VEGFR-2 inhibitors.

Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized and evaluated for anticancer activity against HepG2, HCT-116 and MCF-7 cell lines. MCF-7 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 5d was found to be the most potent derivative overall the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines with IC50 = 8.98 ± 0.1, 7.77 ± 0.1 and 6.99 ± 0.1 µM respectively. Compound 5d exhibited higher activity than sorafenib, (IC50 = 9.18 ± 0.6, 5.47 ± 0.3 and 7.26 ± 0.3 µM respectively), against HepG2 and MCF-7 but exhibited lower activity against HCT116 cancer cell lines respectively. Also, this compound displayed lower activity than doxorubicin, (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 µM respectively), against HepG2 and MCF-7 but higher activity against HCT116 cell lines respectively. Compounds 5b, 5c, 5d, 5e, 5f and 7c are respectively, 5.77, 8.58, 9.54, 5.71, 4.68 and 2.31 fold times more toxic in breast cancer cell lines (MCF-7, the most sensitive cells) than in VERO normal cells. All the synthesized compounds 5a-f and 7a-c were evaluated for their inhibitory activities against VEGFR-2. Among them, compound 5d was found to be the most potent derivative that inhibited VEGFR-2 at IC50 value of 0.10 ± 0.01 µM, which is equipotent to sorafenib IC50 value (0.10 ± 0.02 µM). Compound 5c exhibited excellent activity with IC50 value of 0.12 ± 0.01 µM which nearly equipotent to that of sorafenib. Compounds 5b, 5e and 5f exhibited very good activity with the same IC50 value of 0.14 ± 0.02 µM. Also, compounds 7c and 7b possessed good VEGFR-2 inhibition with IC50 values of 0.16 ± 0.06 and 0.17 ± 0.06 µM respectively which are more than the half activity of that of sorafenib. The data obtained from docking studies were highly correlated with that obtained from the biological screening.

Drying Induced Impact on Composition and Oil Quality of Rosemary Herb, Rosmarinus Officinalis Linn.

The natural drying of Rosmarinus officinalis Linn. herbs severely affects its volatile oil quality and yields, which is reported here for the first time. The oils obtained through hydrodistillation from fresh, one, two, and three-weeks dried herbs were analyzed by gas chromatography-mass spectroscopy (GC-MS) and gas chromatography-flame ionization detector (GC-FID), and the yields were 198 ± 3.45, 168.7 ± 5.11, and 97.8 ± 1.27 mg, respectively, as compared to the internal referral standard of 327 ± 5.91 mg yield of the one-week dried herbs' oil. Camphor, the major constituent, significantly depleted from 20.96% to 13.84%, while bornyl acetate yields increased from 1.42% to 12.46% (p values < 0.0001) in three-weeks drying, reflecting the redox processes undergoing within the oil during drying. Several constituents (25) were found in one-week dried herbs' oil as compared to the fresh, two-, and three-weeks oils, which consisted of 23, 19, and 14 constituents, respectively, leading to the recommendation of the one-week drying of the herb for maximum oil yield. The DPPH (2, 2-diphenyl-1-picryl-hydrazyl) reactivity was highest for the two- and three-weeks dried herb-based oils, followed by the one-week dried- and fresh-herb-based oils (p < 0.0001), again indicating major chemical changes during herbs' dryings, affecting the free-radical scavenging capacity of these batches of oils obtained after different drying times.

Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC.

MYC is one of the most important oncogenes and is overexpressed in the majority of cancers. G-Quadruplexes are noncanonical four-stranded DNA secondary structures that have emerged as attractive cancer-specific molecular targets for drug development. The G-quadruplex formed in the proximal promoter region of the MYC oncogene (MycG4) has been shown to be a transcriptional silencer that is amenable to small-molecule targeting for MYC suppression. Indenoisoquinolines are human topoisomerase I inhibitors in clinical testing with improved physicochemical and biological properties as compared to the clinically used camptothecin anticancer drugs topotecan and irinotecan. However, some indenoisoquinolines with potent anticancer activity do not exhibit strong topoisomerase I inhibition, suggesting a separate mechanism of action. Here, we report that anticancer indenoisoquinolines strongly bind and stabilize MycG4 and lower MYC expression levels in cancer cells, using various biochemical, biophysical, computer modeling, and cell-based methods. Significantly, a large number of active indenoisoquinolines cause strong MYC downregulation in cancer cells. Structure-activity relationships of MycG4 recognition by indenoisoquinolines are investigated. In addition, the analysis of indenoisoquinoline analogues for their MYC-inhibitory activity, topoisomerase I-inhibitory activity, and anticancer activity reveals a synergistic effect of MYC inhibition and topoisomerase I inhibition on anticancer activity. Therefore, this study uncovers a novel mechanism of action of indenoisoquinolines as a new family of drugs targeting the MYC promoter G-quadruplex for MYC suppression. Furthermore, the study suggests that dual targeting of MYC and topoisomerase I may serve as a novel strategy for anticancer drug development.

Upgrading the phenolic content, antioxidant and antimicrobial activities of garden cress seeds using solid-state fermentation by Trichoderma reesei.

AIMS: This study aims to evaluate the impact of solid-state fermentation (SSF) by Trichoderma reesei on the phenolic content, antioxidant and antimicrobial activities of garden cress seeds (GCS). METHODS AND RESULTS: The factorial statistical design was employed to optimize the SSF conditions, incubation time, pH, temperature and moisture, for maximum production of the phenolic content and microbial carbohydrate-cleaving enzymes from GCS. The total phenolic content significantly increased from unfermented GCS (401 mg gallic acid equivalent (GAE) 100 g-1 ) to fermented GCS (3600 mg GAE 100 g-1 ) by ninefold. The total antioxidant activity significantly increased in fermented GCS. Fifteen phenolic compounds were detected in fermented GCS with high concentrations compared to 14 in unfermented GCS using high-performance liquid chromatography. A strong correlation between the production of the carbohydrate-cleaving enzymes and the phenolic content of fermented GCS was observed. The phenolic compounds of fermented GCS showed higher antimicrobial activity. CONCLUSIONS: The fermented GCS is a powerful source of phenolic compounds with high antioxidant potentials, which can be used as dietary supplement and antimicrobial agent. SIGNIFICANCE AND IMPACT OF THE STUDY: Solid-state fermentation is a promising technique used for production of added-value bioactive compounds. SSF increased the total phenolic content and antioxidant activity of GCS several folds compared to germination process, which recently studied.

First example of Azo-Sulfa conjugated chromene moieties: Synthesis, characterization, antimicrobial assessment, docking simulation as potent class I histone deacetylase inhibitors and antitumor agents.

This report presents the development of a novel and primary model of sulfonamide compounds encompassing a chromene azo motif with the intent of becoming applicable for drug candidates in the cases of drug-resistant pathogens. The novel molecules (7a-n) have been synthesized via a two-step reaction. First, 4-((2, 4-dihydroxyphenyl)diazenyl)benzenesulfonamide (3a-e) were obtained through the reaction of their corresponding diazotized 4-aminobenzenesulfonamides (1a-e) with resorcinol, followed by the heterocyclization of 3a-e with arylidenemalononitriles (6a-d). Upon structural identification, the newly synthesized compounds were evaluated for their antibacterial and antifungal activities. Moreover, their cytotoxic screening was performed against three cancer cell lines: HCT-116, HepG-2, and MCF-7. Further examinations were comprised of the inhibitory effect analyses of the novel sulfonamide/chromene derivatives against the HDAC classes and the Tubulin polymerization in order to discern the prime antitumor drug candidates.

Corrective osteotomy and in situ fusion for late-presenting nonunion of lateral condyle fractures of the humerus in adults.

BACKGROUND: Late presentation of lateral condylar fractures of the humerus is not an uncommon problem in children, and to lesser extent, in adults. The various surgical interventions for repairing the fracture, correcting the deformity, or even performing anterior transposition of the ulnar nerve as a single procedure or in combination, especially in adults, is still a controversial topic, with a paucity of literature regarding this. There is a risk of loss of the available preoperative range of motion, nonunion, and avascular necrosis. METHODS: In 19 patients with late presentation of lateral humeral condyle fracture, we assessed the results of only corrective osteotomy and internal fixation with lateral incision without anterior transposition of the ulnar nerve with regard to deformity correction, union, and functional results using the Mayo Elbow Performance Score with at least 24 months of follow-up. All patients (14 men, 5 women; average age, 29.1 years) had Milch type 2, 18 patients presented with cubitus valgus deformity, 1 presented with cubitus varus deformity, and 8 patients had tardy ulnar nerve symptoms. RESULTS: Late-presenting lateral condylar fractures could be managed surgically with our procedure alone even if they have a tardy ulnar neuritis, with excellent results in 17 patients and good results in 2 patients. CONCLUSION: In situ fusion, deformity correction, and internal fixation is a valuable method for the management of late-presenting lateral condylar fractures in adults.

Contemporary cemented versus uncemented hemiarthroplasty for the treatment of displaced intracapsular hip fractures: a meta-analysis of forty-two thousand forty-six hips.

INTRODUCTION: Controversy exists regarding the use of cement for hemiarthroplasty to treat displaced intracapsular hip fractures. The aim of this systematic review and meta-analysis was to compare the clinical outcomes between contemporary cemented and contemporary uncemented hemiarthroplasty for the treatment of displaced femoral neck fractures. METHODS: Literature searches of PubMed, Scopus, Web of Science, and Cochrane Central, up to May 2017, were performed. We included randomized controlled trials (RCTs) and observational studies comparing contemporary cemented with contemporary uncemented hemiarthroplasty. Data were pooled as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) in a meta-analysis model. Studies with the Thompson and Austin Moore prostheses were excluded. RESULTS: A total of 29 studies (9 RCTs and 20 observational studies), with a total of 42,046 hips, were included. Meta-analysis showed that the cemented group was associated with fewer periprosthetic fractures (RR = 0.44, 95% CI [0.21, 0.91]), longer operative time (MD = 11.25 min, 95% CI [9.85, 12.66]), more intraoperative blood loss (MD = 68.72 ml, 95% CI [50.76, 86.69]), and higher heterotopic ossification (RR = 1.79, 95% CI [1.11, 2.88]) compared with the uncemented group. Meta-analysis showed no significant difference in terms of post-operative hip function, hip pain, reoperation rate, prosthetic dislocations, aseptic loosening, wound infection, and hospital stay. CONCLUSIONS: This meta-analysis shows that contemporary cemented prostheses have less intra-operative and post-operative fractures, but longer operative time, more intra-operative blood loss, and heterotopic ossifications. Otherwise, there were no significant differences between both groups.

Correction to: Contemporary cemented versus uncemented hemiarthroplasty for the treatment of displaced intracapsular hip fractures: a meta-analysis of forty-two thousand forty-six hips.

The author name "Muhammad Shawqi" was incorrectly presented as "Muhammad Shawq".

Green analytical chromatographic assay method for quantitation of cyclobenzaprine in tablets, spiked human urine and in-vitro dissolution test.

Cyclobenzaprine hydrochloride, a skeletal muscle relaxant has been determined using an ecofriendly micellar HPLC method in its pure form and tablets. The chromatographic determination was performed using C8 monolithic column (100mm×4.6mm i.d., 5µm particle size) and micellar eluent which was composed of sodium dodecyl sulfate (0.15M), n-propanol (15%), 0.02M orthophosphoric acid (pH 4.5) and 0.3% triethylamine using UV detection of effluent was set at 225nm. The calibration plot showed good linearity over concentration range from 2-40µg/mL. The assay results were statistically validated for linearity, accuracy, precision and specificity according to ICH guidelines. Additionally, regarding USP guidelines, the uniformity of tablets content and in-vitro dissolution test of the tablets was tested using the proposed method. Simple and rapid applicability of the developed method allowed determination of the drug in its pure and tablet dosage forms. Moreover, the major advantage of micellar HPLC technique is to determine the drug in biological fluids without prior extraction steps. Depending on this, the estimation of cyclobenzaprine in spiked human urine was so simple without traditional tedious procedures. The proposed method offers the advantages of sensitivity and simplicity in addition to short analysis time which didn't exceed 6 minutes.