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Pancreatic cancer (PanCa) is one of the deadliest cancers, with limited therapeutic response. Various molecular oncogenic events, including dysregulation of ribosome biogenesis, are linked to the induction, progression, and metastasis of PanCa. Thus, the discovery of new therapies suppressing these oncogenic events and ribosome biogenesis could be a novel therapeutic approach for the prevention and treatment of PanCa. The current study was designed to investigate the anti-cancer effect of honey against PanCa. Our results indicated that honey markedly inhibited the growth and invasive characteristics of pancreatic cancer cells by suppressing the mRNA expression and protein levels of key components of ribosome biogenesis, including RNA Pol-I subunits (RPA194 and RPA135) along with its transcriptional regulators, i.e., UBTF and c-Myc. Honey also induced nucleolar stress in PanCa cells by reducing the expression of various nucleolar proteins (NCL, FBL, and NPM). Honey-mediated regulation on ribosome biogenesis components and nucleolar organization-associated proteins significantly arrested the cell cycle in the G2M phase and induced apoptosis in PanCa cells. These results, for the first time, demonstrated that honey, being a natural remedy, has the potential to induce apoptosis and inhibit the growth and metastatic phenotypes of PanCa by targeting ribosome biogenesis.

Naturally occurring naphthoquinones, shikonin and alkannin, are important ingredients of traditional Chinese medicine Zicao. These constituents are reported to have many therapeutic uses, such as wound healing; scar treatment; and anti-inflammation, anti-acne, anti-ulcer, anti-HIV, anticancer, and antibacterial properties. The primary objective of this investigation was to explore the effect of shikonin and alkannin on Escherichia coli ATP synthase and its cell growth. Shikonin caused complete (100 %) inhibition, and alkannin caused partial (79 %) inhibition of wild-type E. coli ATP synthase. Both caused partial (4 %-27 %) inhibition of ATP synthase with genetically modified phytochemical binding site. The growth inhibition of strains expressing normal, deficient, and mutant ATP synthase by shikonin and alkannin, corroborated the inhibition observed in isolated normal wild-type and mutant ATP synthase. Trivial inhibition of mutant enzymes indicated αR283D, αE284R, βV265Q, and γT273A are essential for formation of the phytochemical binding site where shikonin and alkannin bind. Further, shikonin was a potent inhibitor of ATP synthase than alkannin. The antimicrobial properties of shikonin and alkannin were tied to the binding at phytochemical site of microbial ATP synthase. Selective targeting of bacterial ATP synthase by shikonin and alkannin may be an advantageous alternative to address the antibiotic resistance issue., Competing Interests: Declaration of competing interest Authors declare no conflict of interest in the work presented in manuscript “Inhibition of Escherichia coli ATP synthase and cell growth by shikonin and alkannin” submitted for publication in the International Journal of Biological Macromolecules., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Congenital hypothyroidism due to defects in iodotyrosine deiodinase has variable phenotypes and can present as hypothyroid or with normal thyroid testing. Methods: Whole exome sequencing was performed in individuals from two families originating from different regions of Sudan. Mass spectrometry of urine and serum iodotyrosines was performed on subjects from both families. Results: A novel iodotyrosine deiodinase (IYD) mutation (c.835C>T; R279C) was identified in individuals from two Sudanese families inherited as autosomal recessive. The mutation was identified by multiple in silica analyses to likely be detrimental. Serum and urine monoiodotyrosine (MIT) and diiodotyrosine (DIT) were markedly elevated in the homozygous subjects. Conclusion: Measurement of serum and urine DIT and MIT was more sensitive than that of urine iodine or serum thyroid function tests to determine the effect of the IYD mutation.

Background: Intradermal minoxidil is used as an off-label treatment for patchy non-severe alopecia areata (AA) either alone or in combination with steroids; however, studies estimating its efficacy are still lacking., Objectives: To assess the efficacy of intradermal delivery of minoxidil 5% alone and in combination with intralesional triamcinolone acetonide for treatment of patchy non-severe AA., Patients and Methods: One hundred patches in twenty patients with patchy non-severe AA, five patches for each patient, were included in this prospective intra-patient comparative controlled clinical study. Four comparative patches per each patient were randomly assigned to receive 4 sessions, at a 4-week interval, of one of the following treatments: intralesional triamcinolone acetonide, intralesional minoxidil 5%, combination treatment, or micro-needling. The fifth patch was observed as the negative control. Treatment outcomes were assessed at baseline, and 1 month after treatment ends., Results: Minoxidil intradermal injection was nearly comparable to the micro-needling effect and its combination to steroids had no additive effect. Hair regrowth in response to minoxidil occurred earlier than the spontaneous recovery., Conclusion: Monotherapy of intralesional minoxidil is of limited efficacy in treating non-severe patchy AA, but it speeds the recovery.

Hydroxyethylcellulose (HEC) is a biocompatible, biodegradable, nontoxic, hydrophilic, non- ionic water soluble derivative of cellulose. It is broadly used in biomedical field, paint industry, as a soil amendment in agriculture, coal dewatering, cosmetics, absorbent pads, wastewater treatment and gel electrolyte membranes. Industrial uses of HEC can be extended by the its grafting with different polymers including poly acrylic acid, polyacrylamide, polylactic acid, polyethyleneglycol, polydimethyleamide, polycaprolactone, polylactic acid and dimethylamino ethylmethacrylate. This permits the formation of new biomaterials with improved properties and versatile applications. In this article, a comprehensive overview of graft copolymers of HEC with other polymers/compounds and their applications in drug delivery, stimuli sensitive hydrogels, super absorbents, personal hygiene products and coal dewatering is presented., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The thyroglobulin ( TG ) gene encodes a protein required for thyroid hormone synthesis and iodine storage. Deleterious TG mutations produce congenital hypothyroidism (CH) often presenting with undetectable serum TG. Alu elements, common throughout the human genome, have a poly(dA) region in the 3' end of the strand. Herein two of four siblings of a consanguineous Sudanese family with CH, goiter, high initial serum thyrotropin, and undetectable TG were found to have a novel frameshift insertion of an Alu element within an exon of the TG gene: c.7909ins p.Y3637Ffs. This report demonstrates a novel Alu element insertion within TG causing CH.

Background and Aim: Goat is considered very important ruminant animals that are raised in Jordan; however, the production of the local breeds is low to moderate, and thus, some genetic improvement programs could have a positive effect on the performance of the local breeds. The objective of this study was to investigate the effect of crossing Baladi (BB) goat with Shami., Materials and Methods: A total of 30 newly weaned goat kids (15 BB and 15Shami-Baladi [SB] kids) were evaluated for growth performance and carcass traits. The trial lasted for 77 days (7 days for adaptation and 70 days for data collection). Feed intake was measured on a daily basis; body weight of kids was measured at the beginning of the study and biweekly thereafter. At the end of the trial, kids were slaughtered to examine carcass traits., Results: Dry matter intake, initial weight, final weight, and average daily gain (ADG) were not affected by kid's breed type. In addition, breed type of kids showed no significant effect on feed efficiency (feed:gain). Hot and cold carcass weight and dressing percentage were also not affected by kid's breed type. Kid breed type had no significant effect on shoulder, rack, and legs percentages. However, SB kids had a higher loin cut percentage compared to BB kids. In addition, Musculus longissimus depth was higher for SB kids., Conclusion: Results of this study indicate that crossing SB goat breeds did not have a significant effect on either growth performance or carcass traits. Further studies using reciprocal cross may reveal different results., (Copyright: © Obeidat, et al.)

Background: Unlicensed and off label drug use is an issue recognized worldwide in pediatric pharmacotherapy. The study was designed to assess the prevalence and predictors of unlicensed and off label drug use in neonatal population of Pakistan., Method: A prospective, observation study was conducted in nursery units at pediatric department of four tertiary care hospitals during the 1 year. Micromedex DRUGDEX was used to evaluate the case notes of 1300 patients. Logistic regression was employed to calculate the odds ratio for the predictors of unlicensed and off label drug use., Results: A total of 1300 patients were included in this study who were treated with 52 different drugs. The prevalence of off label drug use was higher (52.14%) as compared to unlicensed drug use (33.35%). Dose (61.29%) and indication (13.68%) were the most frequent reasons for off label prescribing. In comparison to the corresponding reference categories, females and preterm infants were less likely to receive unlicensed prescriptions. While patients staying at hospital more than 5 days and infants receiving 3 or more medications were significantly more likely to receive unlicensed prescriptions. Moreover, in comparison to the corresponding reference categories, females were less likely to receive off label prescriptions while infants receiving 3 or more medications were 7 times more likely to receive off label prescriptions., Conclusion: The significant prevalence of unlicensed and off label drug prescriptions was found in neonatal population of Pakistan. The findings imply that more data on prevalence of unlicensed and off label prescriptions are required to provide a better picture of pediatric therapy in developing countries. Furthermore, advance formulations with new dosing in pediatrics is also necessary to minimize the risk of adverse drug events.

Objectives: To identify contextual barriers (social, cultural, geographic and economic), faced by Lady Health Workers (LHWs) and to assess their strategies at different levels (individual, community and system) in the provision of family planning services to their clients in Tehsil Gujar Khan., Methods: The mixed model cross-sectional study was conducted from April 1 to July 10, 2010, in Tehsil Gujar Khan, Punbjab, Pakistan. It was carried out in two phases: in the first phase 10 in-depth interviews were conducted with the workers, followed by two focus group discussions. On the basis of findings, a structured questionnaire was developed and administered to 111 workers in the second phase. Of the total, 97 responses were used for analysis. Data analysis was done by SPSS-16., Results: Majority of the respondents reported barriers at the community level: religious barriers 69% (n = 67), sociocultural barriers 58% (n = 56), transport 54% (n = 52), communication and economic reasons 25% (n = 24). Individual level barriers were female gender, experience and low education. System-level barriers were increased workload, National immunization days/sub-national immunization days, late supply, stock shortage (especially injectables), problems for referred clients and lack of proper incentives., Conclusion: Lady health workers still face barriers at individual, family, community and system level in the delivery of Family Planning services.

Synthetic nanosized Zn-Al-hydrotalcite (Zn-Al-HT) with 20 nm crystallite size and 61 m(2)/g BET-surface area is found to be a mild and efficient catalyst for N-sulfonylation of amines in quantitative yields under ultrasound irradiation. Exclusive synthesis of sulfonamides, using Zn-Al-HT, under ultrasound irradiation, was realized by compatible basic sites of catalyst used. The products were isolated after simple work-up in high yields and purity., (Copyright © 2010 Elsevier B.V. All rights reserved.)