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Introduction: Improving feed efficiency (FE) is a significant goal in animal breeding programs. Variations in FE and its relationship with rumen microbiota remain poorly understood across different goat breeds., Methods: This study assessed the influence of the rumen microbiome and host genome on FE in 10 Shami (SH) goats and 10 Zaraibi (ZA) goats, all of which were fed the same diet. The animals were genotyped using the Illumina 65KSNP chip arrays v2 , and their rumen bacteria and archaea were investigated using PCR-amplicon sequencing of the 16S rRNA gene., Results: The results showed that the ZA goats exhibited higher FE than the SH goats ( p < 0.05) and a greater relative abundance ( p < 0.05) of rumen bacterial groups that are involved in the degradation of cellulose and hemicelluloses, such as Bacteroidota and Fibrobacterota, along with genera such as Prevotella , Lachnospiraceae AC2044 group, Lachnospiraceae NK3A20 group, and Succiniclasticum , which are linked to carbohydrate and nitrogen metabolism pathways. In addition, breed differences were found to affect the proportions of milk fatty acids. The association analysis identified 26 genome windows containing several putative candidate genes, such as TMEM241 , AP4S1 , FTO , HYAL2 , BBS2 , CD52 , CRYBG2 , PIGV , WDTC1 , EEF1A2 , GBA2 , FNIP1 , ACSL6 , STARD10 , VPS26B , ACAD8 , GLB1L3 , NRN1L , LCAT , and SLC7A6 . These genes contributed to FE traits in Egyptian goats, as they are involved in obesity, metabolism, and the transport of energy, vitamins, fatty acids, proteins, and lipids through diverse biological pathways., Discussion: This study suggests that specific genetic markers and rumen microbial traits could be used to identify high-efficient individuals in Egyptian goat breeds, and improving breeding strategies for FE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Rabee, Abou-souliman, Yousif, Lamara, El-Sherbieny, Elwakeel and Sallam.)

Brucellosis is a highly contagious zoonotic bacterial disease. It has considerable negative consequences on the animal production industry worldwide. The objective of this study was to investigate the genetic and molecular variations in Shami goat susceptible to Brucella infection. Blood samples were collected from fifty mature Shami goats (30 Brucella-infected does and 20 non-infection). DNA was extracted and selected parts the immunity; solute carrier family 11 member 1 (SLC11A1), toll-like receptor 1 (TLR1), toll-like receptor 9 (TLR9), SP110 nuclear body protein (SP110), the adenosine A3 receptor (ADORA3), caspase activating recruitment domain 15 (CARD15) and interferon regulatory factor 3 (IRF3), antioxidant glutathione peroxidase 1 (GPX1), nitric oxide synthase (NOS), NAD(P)H dehydrogenase [quinone] 1 (NQO1) and transcription factor NF-E2-related factor 2 (Nrf2) and erythritol related transketolase (TKT), ribose 5-phosphate isomerase (RPIA) and Adenosine monophosphate deaminase (AMPD) genes were sequenced. Likewise, the levels of gene expressions were investigated. The results identified polymorphic variants between healthy and infected does. Levels of gene expression of SLC11A1, TLR1, TLR9, SP110, ADORA3, CARD15, IRF3, HMOX1, TKT, RPIA and AMPD were significantly (P < 0.05) up regulated in the infected compared to the non-infected ones. On the other hand, GPX1, NOS, NQO1 and Nrf2 genes were significantly (P < 0.05) downregulated in the infected compared to the non-infected does. The results of serum profile indicated that there is a significant (P < 0.05) increase in the activities of AST, ALT, GGT, LDH, ALP as well as serum level of globulin, triglycerides, cholesterol, MDA, NO, IL-1β, TNF-α, IgM, IgG, haptoglobin and amyloid A. On the other hand, there were significant reductions in the glucose, total protein albumin, urea, calcium, inorganic phosphorus, sodium, copper, zinc, iron, TAC, GSH, SOD, GPx, IL-10 and fibrinogen in the infected compared to the non-infected does. Our results provide valuable information about the serum profile variations and putative genetic markers for Brucella infection in goats. This could be utilized in controlling goat brucellosis through selective breeding of natural resistant animals., Competing Interests: Declarations. Ethics approval and consent to participate: All animal procedures included in the current study were approved by the Animal Breeding Ethics Committee at the Desert Research Center (DRC) in Egypt (Project ID: 43213) with approval reference number AB/NO2022. All methods were performed in accordance with the relevant guidelines and regulations, and in compliance with the ARRIVE guidelines. In addition, the project does not include euthanasia of the experimental animals. Sample size was decided based on the availability of similar animals with similar physical and physiological status. Competing interests: The authors declare that they have no conflict of interest., (© 2025. The Author(s).)

In the current comprehensive review, we first highlighted circRNAs, which are key ncRNAs. Next, we discussed the relationships among circRNAs and breast cancer subtypes via in silico databases analysis and extensive literature search. CircRNAs, that sponge miRNA axes or act as silencers of oncogenic mRNAs, have been extensively addressed in the context of this review. During BC pathogenesis, the circRNA/microRNA/messenger RNA (mRNA) axis plays a major role in disease growth, progression, and survival/resistance and could be targeted for improved treatment options. This review also aimed to address oncogenic and tumor suppressor mRNAs, which are regulated by various circRNAs in BC. Moreover, we mentioned the relation of different circRNAs with cancer hallmarks, patient survival together with drug resistance. Additionally, we discussed circRNAs as vaccines and biomarkers in BC. Finally, we studied exosomal circRNAs as a hot interesting area in the research. REVIEW SIGNIFICANCE: Via using in silico databases, bioinformatics analysis, and a thorough literature search to first highlight circRNA as a crucial ncRNA and its biogenesis, and then we explored the connection between circRNA and breast illnesses. In the framework of the review, circRNA sponged-miRNAs axis or as silencers to oncogenic mRNAs were extensively discussed. In the pathophysiology of BC, the circular RNA/microRNA/messenger RNA axis is crucial for the propagation of the disease and resistance that may be targeted for more effective treatment options, in order to confront tumor suppressor and oncogenic mRNAs that are presently regulated by circRNAs in BC. For better patient results, we advised further mechanistic research to elucidate additional ncRNA axis that may be targeted for the therapy of BC and for prognosis/ or early diagnosis., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In livestock, identifying the physiological and reproductive stages is valuable in guiding management decisions related to nutrition, veterinary procedures, and breeding programs. To achieve this goal, a cohort of Barki ewes in this research underwent observation across three pivotal physiological conditions: pre-pregnancy, late pregnancy, and early lactation. Blood samples were collected to investigate the changes in serum metabolic profile as well as gene expression pattern of cytokines and antioxidants markers during these stages., Results: Our results showed that during late pregnancy, there was a significant (P < 0.05) increase in red blood cells (11.9 ± 0.5 10 12 /L), hemoglobin (10.8 ± 0.4 g/dl) and neutrophils count (7 ± 0.1 10 9 /L) with significant decrease (P < 0.05) of total white blood cell count (9.1 ± 0.05 10 9 /L). The packed cell volume (%) and monocyte count showed a significant (P < 0.05) decrease during both late pregnancy and early lactation stages. The serum concentrations of glucose, cholesterol, GSH, GPx, SOD and catalase displayed significant (P < 0.05) decrease during late pregnancy and early-lactation. Notably, during late pregnancy, there was a significant (P < 0.05) increase in the serum concentrations of albumin, globulin, urea, IGF-1, and malondialdehyde with significant decrease (P < 0.05) of total protein (4.9 ± 0.08 g/dl). Additionally, during early lactation, there was a significant (P < 0.05) increase in the serum levels of non-esterified fatty acids, triiodothyronine (T3), and thyroxin (T4). The gene expression profiles of cytokines (IL-4, IL-6, IL-8, and NFKB) were decreased in the ewes during late pregnancy compared to pre-pregnant and early lactation stages. In addition, the expression profile of antioxidant genes (SOD, CAT, GPX, and Nrf2) was significantly upsurged in the non-pregnant ewes compared to late pregnancy and early lactation ones., Conclusions: The results concluded that different physiological status significantly affects the blood metabolic profile and gene expression pattern in Barki sheep. Our findings can be helpful in monitoring animal health and applying in breeding programs of Barki sheep under harsh environmental conditions., (© 2024. The Author(s).)

Background: In elderly patients with external full-thickness rectal prolapse (EFTRP), the exact differences in postoperative recurrence and functional outcomes between laparoscopic ventral mesh rectopexy (LVMR) and perineal stapler resection (PSR) have not yet been investigated., Methods: We conducted a retrospective multicenter study on 330 elderly patients divided into LVMR group (n = 250) and PSR (n = 80) from April 2012 to April 2019. Patients were evaluated before and after surgery by Wexner incontinence scale, Altomare constipation scale, and patient satisfaction questionnaire. The primary outcomes were incidence and risk factors for EFTRP recurrence. Secondary outcomes were postoperative incontinence, constipation, and patient satisfaction., Results: LVMR was associated with fewer postoperative complications (p < 0.001), lower prolapse recurrence (p < 0.001), lower Wexner incontinence score (p = 0.03), and lower Altomare's score (p = 0.047). Furthermore, LVMR demonstrated a significantly higher surgery-recurrence interval (p < 0.001), incontinence improvement (p = 0.019), and patient satisfaction (p < 0.001) than PSR. Three and 13 patients developed new symptoms in LVMR and PSR, respectively. The predictors for prolapse recurrence were LVMR (associated with 93% risk reduction of recurrence, OR 0.067, 95% CI 0.03-0.347, p = 0.001), symptom duration (prolonged duration was associated with an increased risk of recurrence, OR 1.131, 95% CI 1.036-1.236, p = 0.006), and length of prolapse (increased length was associated with a high recurrence risk (OR = 1.407, 95% CI = 1.197-1.655, p < 0.001)., Conclusions: LVMR is safe for EFTRP treatment in elderly patients with low recurrence, and improved postoperative functional outcomes., Trial Registration: Clinical Trial.gov (NCT05915936), retrospectively registered on June 14, 2023., (© 2024. The Author(s).)

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Unstable sacral fractures with pelvic fractures are challenging to both surgeons and patients, particularly in the immediate post-injury phase and later when definitive fixation is undertaken. Percutaneous iliosacral screw fixation is widely regarded as the gold standard treatment for unstable sacral fractures without spinopelvic dissociation. Closed reduction and percutaneous fixation using iliosacral screws for sacral fractures provide early stabilisation without the need for extensive surgical exposure, thereby mitigating major complications associated with open surgical procedures. A new technique for stabilising unstable sacral fractures is the minimally invasive ilioilial fixator, also called a transiliac internal fixator (TIIF), which has gained more attention for its ability to address challenges associated with sacroiliac screw fixation. The objective of this study is to compare the functional, radiological, and surgical outcomes between the percutaneous iliosacral screw and the ilioilial fixator., Methods: A total of 51 patients with sacral fracture injuries sustained between August 2019 and November 2021 were included in this study, with 25 patients in Group A and 26 patients in Group B. Patient randomization was done using computer-generated randomization facilitated by Random Allocation Software (Mahmood Saghaei, Isfahan, Iran). All patients underwent the chosen intervention within 10 days of the trauma. Patients had follow-up at two weeks, six weeks, and 12 months post-treatment. The results of fixation were evaluated radiologically based on the Matta and Tornetta grading system and clinically using the Majeed pelvic scoring system. Complications were detected in both groups during follow-up visits., Results: The study found no statistically significant differences between the two patient groups in terms of final clinical assessment (p=0.79), radiological assessment (p=0.78), or the need for another operation (p=1.0). Moreover, there were no statistically significant differences between the groups with respect to complication rates (p=0.63) or the time of union (p=0.14). No differences were noted in terms of intraoperative blood loss (p=0.93) or operative time (p=0.34) but for longer incision length in the ilioilial fixator group (p<0.001) and an increased risk of intraoperative radiation exposure in the iliosacral screw group (p<00.1)., Discussion: Although the iliosacral screw is considered a gold standard for unstable sacral fracture, a TIIF is a good alternative with a very satisfactory outcome., Conclusion: Although the iliosacral screw still remains the gold standard for the management of sacral fractures, the ilioilial fixator emerges as a good alternative with comparable functional and radiological outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shaalan et al.)

This work is mainly concerned with the effect of anthropogenic activities and natural radioactivity due to the presence of highly radioactive black sand spots, factory construction, and shipping, in addition to other activities like agriculture on human beings. Forty samples were collected along Baltim-El Burullus coastal plain to detect the effect of these problems and determine the suggested solutions. The black sand of the Baltim-El Burullus coastal plain exhibits a considerable amount of economically heavy minerals, their ratio relative to the bulk composition in the investigated samples ranges from 3.18 to 10.5% with an average of 5.45%. The most important of them are magnetite, ilmenite, rutile, leucoxene, garnet, zircon and monazite. The existence of some radioactive-bearing accessory mineral deposits like zircon and monazite led to measuring the naturally occurring radionuclides 226 Ra, 232 Th and 40 K to evaluate the excess lifetime cancer risk (ELCR). The results showed that these concentrations are 19.1 ± 9.73, 14.7 ± 9.53 and 211 ± 71.34 Bq kg -1 were lower than the corresponding reported worldwide average of 35, 45, and 412 Bq kg -1 for each radionuclide ( 226 Ra, 232 Th, and 40  K). The gamma hazard indices such as absorbed dose rate (D air ), the annual effective dose (AED), and excess lifetime cancer risk (ELCR) factor were computed in the investigated sediments and all the results were found (D air  = 26.4 nGy h -1 , AED = 0.03 mSv year -1 , ELCR = 0.0001) to be lower than the values suggested by the United Nations Scientific Committee on the effect of Atomic Research (59 nGy h -1 , 0.07 mSv year -1 and 0.0029 for D air , AED and ELCR, respectively). The study suggests that the black sand is safe to use in various infrastructure applications at Baltim-El Burullus coastal plain. The levels of radioactivity are not high enough to pose a risk to human health., (© 2024. The Author(s).)

microRNAs (miRNAs) play a crucial role in brain growth and function. Hence, research on miRNA has the potential to reveal much about the etiology of neuropsychiatric diseases. Among these, schizophrenia (SZ) is a highly intricate and destructive neuropsychiatric ailment that has been thoroughly researched in the field of miRNA. Despite being a relatively recent area of study about miRNAs and SZ, this discipline has advanced enough to justify numerous reviews that summarize the findings from the past to the present. However, most reviews cannot cover all research, thus it is necessary to synthesize the large range of publications on this topic systematically and understandably. Consequently, this review aimed to provide evidence that miRNAs play a role in the pathophysiology and progression of SZ. They have also been investigated for their potential use as biomarkers and therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Goats contribute significantly to the global food security and industry. They constitute a main supplier of meat and milk for large proportions of people in Egypt and worldwide. Brucellosis is a zoonotic infectious disease that causes a significant economic loss in animal production. A case-control genome-wide association analysis (GWAS) was conducted using the infectious status of the animal as a phenotype. The does that showed abortion during the last third period of pregnancy and which were positive to both rose bengal plate and serum tube agglutination tests, were considered as cases. Otherwise, they were considered as controls. All animals were genotyped using the Illumina 65KSNP BeadChip. Additionally, the diversity and composition of vaginal and fecal microbiota in cases and controls were investigated using PCR-amplicone sequencing of the V4 region of 16S rDNA. After applying quality control criteria, 35,818 markers and 66 does were available for the GWAS test. The GWAS revealed a significantly associated SNP (P = 5.01 × 10 -7 ) located on Caprine chromosome 15 at 29 megabases. Four other markers surpassed the proposed threshold (P = 2.5 × 10 -5 ). Additionally, fourteen genomic regions accounted for more than 0.1% of the variance explained by all genome windows. Corresponding markers were located within or in close vicinity to several candidate genes, such as ARRB1, RELT, ATG16L2, IGSF21, UBR4, ULK1, DCN, MAPB1, NAIP, CD26, IFIH1, NDFIP2, DOK4, MAF, IL2RB, USP18, ARID5A, ZAP70, CNTN5, PIK3AP1, DNTT, BLNK, and NHLRC3. These genes play important roles in the regulation of immune responses to the infections through several biological pathways. Similar vaginal bacterial community was observed in both cases and controls while the fecal bacterial composition and diversity differed between the groups (P < 0.05). Faeces from the control does showed a higher relative abundance of the phylum Bacteroidota compared to cases (P < 0.05), while the latter showed more Firmicutes, Spirochaetota, Planctomycetota, and Proteobacteria. On the genus level, the control does exhibited higher abundances of Rikenellaceae RC9 gut group and Christensenellaceae R-7 group (P < 0.05), while the infected does revealed higher Bacteroides, Alistipes, and Prevotellaceae UCG-003 (P < 0.05). This information increases our understanding of the genetics of the susceptibility to Brucella in goats and may be useful in breeding programs and selection schemes that aim at controlling the disease in livestock., (© 2023. The Author(s).)

Background: Laparoscopic Nissen fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (>5 cm) with severe GERD (DeMeester score >100)., Materials and Methods: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery., Results: Three hundred sixty patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9 vs. 8.3%) and recurrent regurgitation (2.2 vs. 5%) showed a lower incidence in the LNF+ group ( P =0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0 vs. 3.3% and 0 vs. 2.8% cases in the LNF+ and LNF groups, respectively ( P =0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75 vs. 5.6% and 0 vs. 3.9% of patients ( P =0.001). Score III postoperative persistent dysphagia was 0 vs. 2.8% in the two groups ( P =0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3 vs. 86.7% in both cohorts, respectively ( P =0.05)., Conclusions: Intraoperative high-resolution manometry and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Understanding the genomic features of livestock is essential for successful breeding programs and conservation. This information is scarce for local goat breeds in Egypt. In the current study, genomic regions with selection signatures were identified as well as runs of homozygosity (ROH), genomic inbreeding coefficients (F ROH ) and fixation index (F ST ) were detected in Egyptian Nubian, Damascus, Barki and Boer goat breeds. A total of 46,268 SNP markers and 337 animals were available for the genomic analyses. On average, 145.44, 42.02, 87.90 and 126.95 ROHs were detected per individual in the autosomal genome of the respective breeds. The mean accumulative ROH lengths ranged from 46.5 Mb in Damascus to 360 Mb in Egyptian Nubian. The short ROH segments (< 2 Mb) were most frequent in all breeds, while the longest ROH segments (> 16 Mb) were exclusively found in the Egyptian Nubian. The highest average F ROH was observed in Egyptian Nubian (~ 0.12) followed by Boer (~ 0.11), while the lowest F ROH was found in Damascus (~ 0.05) and Barki breed (~ 0.03). The estimated mean F ST was 0.14 (Egyptian Nubian and Boer), 0.077 (Egyptian Nubian and Barki), 0.075 (Egyptian Nubian and Damascus), 0.071 (Barki and Boer), 0.064 (Damascus and Boer), and 0.015 (Damascus and Barki), for each pair of breeds. Interestingly, multiple SNPs that accounted for high F ST values were observed on chromosome 6 in regions harboring ALPK1 and KCNIP4. Genomic regions overlapping both F ST and ROH harbor genes related to immunity (IL4R, PHF23, GABARAP, GPS2, and CD68), reproduction (SPATA2L, TNFSF12, TMEM95, and RNF17), embryonic development (TCF25 and SOX15) and adaptation (MC1R, KDR, and KIT), suggesting potential genetic adaptations to local environmental conditions. Our results contribute to the understanding of the genetic architecture of different goat breeds and may provide valuable information for effective preservation and breeding programs of local goat breeds in Egypt., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Drug-induced acute kidney injury (AKI) represents a potentially serious disorder associated with increased morbidity and mortality. The presented study investigated the ability of the oral antidiabetic agent, dapagliflozin (DAPA), to preserve the kidneys of rats subjected to vancomycin (VCM)-induced AKI. Rats were injected with VCM (400 mg/kg; i.p daily) for 7 successive days to induce AKI. Rats that received VCM were pretreated with DAPA at 5 or 10 mg/kg; p.o daily for 14 successive days. Vancomycin-treated rats depicted renal tubular damage, decline in renal function, and renal morphological alterations. Impairment of renal antioxidant machinery and propagation of renal cell apoptosis was apparent in the setting of VCM overdose. Pretreatment of VCM rats with DAPA, particularly at 10 mg/kg, effectively attenuated NADPH oxidase-4 (NOX4)-induced renal ROS, hampered activin A activation, and repressed miRNA-21/PTEN/pAKT signaling. These events were associated with impeding the expression of renal p-FOXO3a/t-FOXO3a ratio and promoting the nuclear localization of FOXO3a immnoexpression, enhancing renal antioxidant enzymes. At the same time, DAPA pretreatment improved renal function indices and alleviated the kidney injury markers, NGAL, and KIM-1, accompanied by restoring the normal renal histopathological structure. Regarding renal apoptosis, DAPA suppressed the expression of Bax/Bcl2 ratio and caspase-3. This study demonstrates that DAPA ameliorates VCM-induced AKI in rats via modulating renal oxidative stress, presumably by interfering with NOX4/activin A/miRNA-21 cascade and augmenting t-FOXO3a expression as well as dampening renal cell apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Testicular germ cell tumors (TGCTs) are the most common testicular neoplasms in adolescents and young males. Understanding the genetic basis of TGCTs represents a growing need to cope with the increased incidence of these neoplasms. Although the cure rates have been comparatively increased, investigation of mechanisms underlying the incidence, progression, metastasis, recurrence, and therapy resistance is still necessary. Early diagnosis and non-compulsory clinical therapeutic agents without long-term side effects are now required to reduce the cancer burden, especially in the younger age groups. MicroRNAs (miRNAs) control an extensive range of cellular functions and exhibit a pivotal action in the development and spreading of TGCTs. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of TGCTs by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative perspective, cell cycle dysregulation, apoptosis disruption, stimulation of angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and resistance to certain treatments. Herein, we present an up-to-date review of the biogenesis of miRNAs, miRNA regulatory mechanisms, clinical challenges, and therapeutic interventions of TGCTs, and role of nanoparticles in the treatment of TGCTs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Long non-coding RNAs (lncRNAs) are a class of noncoding RNAs with a length larger than 200 nucleotides that participate in various diseases and biological processes as they can control gene expression by different mechanisms. Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by symmetrical destructive destruction of distal joints as well as extra-articular involvement. Different studies have documented and proven the abnormal expression of lncRNAs in RA patients. Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating RA. This review will focus on RA pathogenesis, clinical implications, and related lncRNA expressions that help to identify new biomarkers and treatment targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Cholangiocarcinoma (CCA), the second most frequent liver cancer after hepatocellular carcinoma, has been rising worldwide in recent epidemiological research. This neoplasia's pathogenesis is poorly understood. Yet, recent advances have illuminated the molecular processes of cholangiocyte malignancy and growth. Late diagnosis, ineffective therapy, and resistance to standard treatments contribute to this malignancy's poor prognosis. So, to develop efficient preventative and therapy methods, the molecular pathways that cause this cancer must be better understood. MicroRNAs (miRNAs) are non-coding ribonucleic acids (ncRNAs) that influence gene expression. Biliary carcinogenesis involves abnormally expressed miRNAs that act as oncogenes or tumor suppressors (TSs). The miRNAs regulate multiple gene networks and are involved in cancer hallmarks like reprogramming of cellular metabolism, sustained proliferative signaling, evasion of growth suppressors, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, and avoidance of immune destruction. In addition, numerous ongoing clinical trials are demonstrating the efficacy of therapeutic strategies based on miRNAs as powerful anticancer agents. Here, we will update the research on CCA-related miRNAs and explain their regulation involved in the molecular pathophysiology of this malignancy. Eventually, we will disclose their potential as clinical biomarkers and therapeutic tools in CCA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

MicroRNAs (miRNAs), short, highly conserved non-coding RNA, influence gene expression by sequential mechanisms such as mRNA breakdown or translational repression. Many biological processes depend on these regulating substances, thus changes in their expression have an impact on the maintenance of cellular homeostasis and result in the emergence of a variety of diseases. Relevant studies have shown in recent years that miRNAs are involved in many stages of bone development and growth. Additionally, abnormal production of miRNA in bone tissues has been closely associated with the development of numerous bone disorders, such as osteonecrosis, bone cancer, and bone metastases. Many pathological processes, including bone loss, metastasis, the proliferation of osteosarcoma cells, and differentiation of osteoblasts and osteoclasts, are under the control of miRNAs. By bringing together the most up-to-date information on the clinical relevance of miRNAs in such diseases, this study hopes to further the study of the biological features of miRNAs in bone disorders and explore their potential as a therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function post-transcriptionally to regulate gene expression by binding to particular mRNA targets and causing destruction of the mRNA or translational inhibition of the mRNA. The miRNAs control the range of liver activities, from the healthy to the unhealthy. Considering that miRNA dysregulation is linked to liver damage, fibrosis, and tumorigenesis, miRNAs are a promising therapeutic strategy for the evaluation and treatment of liver illnesses. Recent findings on the regulation and function of miRNAs in liver diseases are discussed, with an emphasis on miRNAs that are highly expressed or enriched in hepatocytes. Alcohol-related liver illness, acute liver toxicity, viral hepatitis, hepatocellular carcinoma, liver fibrosis, liver cirrhosis, and exosomes in chronic liver disease all emphasize the roles and target genes of these miRNAs. We briefly discuss the function of miRNAs in the etiology of liver diseases, namely in the transfer of information between hepatocytes and other cell types via extracellular vesicles. Here we offer some background on the use of miRNAs as biomarkers for the early prognosis, diagnosis, and assessment of liver diseases. The identification of biomarkers and therapeutic targets for liver disorders will be made possible by future research into miRNAs in the liver, which will also help us better understand the pathogeneses of liver diseases., Competing Interests: Competing interests The authors declare they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Epigenetic modifications play a pivotal role in autoimmune/inflammatory disorders and could establish a bridge between personalized medicine and disease epidemiological contexts. We sought to investigate the role of epigenetic modifications beside genetic alterations in the MEFV gene in familial Mediterranean fever (FMF). The study comprised 63 FMF patients diagnosed according to the Tel Hashomer criteria: 37 (58.7%) colchicine-responders, 26 (41.3%) non-responders, and 19 matched healthy controls. MEFV mutations were detected using a CE/IVD-labeled 4-230 FMF strip assay. DNA methylation of MEFV gene exon 2 was measured using bisulfite modification and related to pyrin level, phenotypic picture, MEFV mutations, disease severity, serum amyloid A (SAA), CRP, ESR, disease severity, and colchicine response. Our results showed that FMF patients exhibited significantly higher methylation percentage (p < 0.001) and lower pyrin levels (p < 0.001) compared to the control. The MEFV gene M694I mutation was the most commonly reported mutation (p < 0.004). High methylation percentage of the MEFV exon 2 and low pyrin concentration were correlated with disease severity, high SAA, ESR levels, H-pylori, and renal calculi. In conclusion, this study highlights the relation between high methylation percentage, reduced pyrin level, and different biomarkers in FMF, which underscores their role in the pathogenesis of FMF and could be considered as potential therapeutic targets.

Purpose: Combined anterior and posterior ring (APR) fixation is classically performed in Tile B2 and C1 injuries to achieve superior biomechanical stability. However, the posterior ring (PR) is the main weight bearing portion that is responsible for weight transmission from the upper parts of the body to the lower limbs through the sacrum and the linea terminalis. It is hypothesized that isolated PR fixation can achieve comparable radiological and clinical outcomes to APR fixation. Therefore, we conducted this study to compare the two fixation principles in managing Tile B2 and C1 injuries., Methods: Our study included 20 patients with Tile B2 injuries and 20 patients with Tile C1 injuries. This study was a randomized control single-blinded study via computerized random numbers with a 1:1 allocation by using random block method. The study was performed at a level one trauma center. A total of 40 patients with Tile B2 and C1 injuries underwent combined APR or isolated PR fixation (Group A and B, respectively). Matta & Tornetta radiological principles and Majeed pelvic scoring system were used for the assessment of primary outcomes and postoperative complications. Secondary outcomes included operative time, amount of blood loss, intraoperative assessment of reduction, need of another operation, length of hospital stay, ability to weight bear postoperatively and pain control metrics. We used student t-test to compare the difference in means between two groups, and Chi-square test to compare proportions between two qualitative parameters. We set the confidence interval to 95% and the margin of error accepted to 5%. So, p ≤ 0.05 was considered statistically significant., Results: The mean follow-up duration was 18 months. The operative time (mean difference 0.575 h) and the intraoperative blood loss (mean difference 97.5 mL) were lower in Group B. Also, despite the higher frequency of rami displacement before union in the same group, there were no significant differences in terms of radiological outcome (excellent outcome with OR = 2.357), clinical outcome (excellent outcome with OR = 2.852) and postoperative complications assessment (OR = 1.556) at last follow-up., Conclusion: The authors concluded that isolated PR fixation could favorably manage Tile B2 and C1 pelvic ring injuries with Nakatani zone II pubic rami fractures and intact inguinal ligament. Its final radiological and clinical outcomes and postoperative complications were comparable to combined APR fixation, but with less morbidity (shorter operation time, lower amount of blood, and no records of postoperative wound infection)., (Copyright © 2022 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the most common cancer in women and poses a serious threat to their health. Despite familiarity with factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected previous aspects affecting BC progression and treatment in the last decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting the translation of the target mRNA. miRNAs play a crucial role in BC pathogenesis by promoting cancer stem cell (CSCs) proliferation, postponing apoptosis, continuing the cell cycle, and endorsing invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important BC-related molecular pathways such as the PI3K/AKT/mTOR signaling pathway, the Wnt/β-catenin system, JAK/STAT signaling pathway, and the MAPK signaling pathway. Moreover, miRNAs affect the treatment response of BC to chemo and radiotherapy. Consequently, this review aims to provide an acquainted summary of oncomiRs and tumor suppressor (TS) miRNAs and their potential role in BC pathogenesis and therapy responses by focusing on the molecular pathways that drive them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the current work, we designed and synthesized three families of non-fused and fused compounds based on cyanopyridone: derivatives of 6-amino-1,2-dihydropyridine-3,5-dicarbonitrile ( 5a-f ) and 3,4,7,8-tetrahydro pyrimidine-6-carbonitrile ( 6a-b and 7a-e ). The newly synthesized compounds' structure were determined using a variety of techniques, including 1 H NMR, 13 C NMR, mass spectrum, infrared spectroscopy, and elemental analysis. The developed compounds were tested for the ability to inhibit the growth of breast adenocarcinoma (MCF-7) and hepatic adenocarcinoma (HepG2) cell lines using MTT assay. Some of the synthesized compounds were more effective towards the cancer cell lines than the standard treatment taxol. The best antiproliferative activities were demonstrated by non-fused cyanopyridones 5a and 5e against the MCF-7 cell line (IC 50 = 1.77 and 1.39 μM, respectively) and by compounds 6b and 5a against the HepG2 cell line (IC 50 = 2.68 and 2.71 μM, respectively). We further explored 5a and 5e , the two most potent compounds against the MCF-7 cell line, for their ability to inhibit VEGFR-2 and HER-2. Finally, docking and molecular dynamics simulations were performed as part of the molecular modeling investigation to elucidate the molecular binding modes of the tested compounds, allowing for a more thorough comprehension of the activity of compounds 5a and 5e .

Traditional cancer treatments include surgery, radiation, and chemotherapy. According to medical sources, chemotherapy is still the primary method for curing or treating cancer today and has been a major contributor to the recent decline in cancer mortality. Nanocomposites based on polymers and metal nanoparticles have recently received the attention of researchers. In the current study, a nanocomposite was fabricated based on carboxymethyl cellulose and silver nanoparticles (CMC-AgNPs) and their antibacterial, antifungal, and anticancer activities were evaluated. The antibacterial results revealed that CMC-AgNPs have promising antibacterial activity against Gram-negative ( Klebsiella oxytoca and Escherichia coli ) and Gram-positive bacteria ( Bacillus cereus and Staphylococcus aureus ). Moreover, CMC-AgNPs exhibited antifungal activity against filamentous fungi such as Aspergillus fumigatus , A. niger , and A. terreus. Concerning the HepG2 hepatocellular cancer cell line, the lowest IC 50 values (7.9 ± 0.41 µg/mL) were recorded for CMC-AgNPs, suggesting a strong cytotoxic effect on liver cancer cells. As a result, our findings suggest that the antitumor effect of these CMC-Ag nanoparticles is due to the induction of apoptosis and necrosis in hepatic cancer cells via increased caspase-8 and -9 activities and diminished levels of VEGFR-2. In conclusion, CMC-AgNPs exhibited antibacterial, antifungal, and anticancer activities, which can be used in the pharmaceutical and medical fields.

The objective of this study was to investigate the genetic polymorphisms in the keratin-associated protein ( KAP22-1 ) gene in Barki ( n = 206 ), Rahmani ( n = 28 ) and Ossimi ( n = 28 ) as the three major sheep breeds in Egypt. Subsequently, the detected variants were correlated with important wool traits. The traits included greasy fleece weight (GFW, g), staple length (SL, cm), prickle factor (PF, %), medullated fiber (MF, %), fiber diameter (FD, µ m), crimp percentage (CR, %) and the standard deviation of FD (SD fd , µ m), as well as the subjectively assessed traits of kemp score (KS), handle grade (HG), greasy color grade (GCG), bulk grade (BG), luster grade (LG) and staple structure (SST). Animals were genotyped by polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP). Five SSCP banding patterns representing three different nucleotide variants (A, B and C) were detected. DNA sequencing confirmed three single nucleotide polymorphisms (SNPs). Animal age significantly affected GFW ( P = 0.007 ), SD fd ( P = 0.006 ), SL ( P = 0.002 ), CR ( P = 0.006 ), KS ( P = 0.001 ), LG ( P = 0.006 ) and SST ( P = 0.013 ). Likewise, the breed had a significant effect on all studied traits except HG and BG, which was not significant. Results showed significant associations between the KAP22-1 variants and CR ( P = 0.01 ), SL ( P = 0.012 ), KS ( P < 0.001 ) and GCG ( P = 0.01 ). Interestingly, animals with BB genotypes tended to produce more wool yield ( 1163.63 ± 65.91  g) with high SL ( 8.38 ± 0.20  cm), CR ( 8.38 ± 0.21  %) and KS ( 1.98 ± 1.88 ). Results of this study strongly recommend the KAP22-1 gene as a candidate gene for wool production traits in Egyptian sheep, with new useful insights into the visually assessed wool traits. The identified genetic markers may be incorporated into breeding strategies and genetic improvement programs of wool traits in Egyptian sheep., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2022 Ahmed M. Sallam et al.)

Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Consequently, dysregulation and disruption in their function, miRNAs are linked to CRC malignant pathogenesis by controlling several cellular processes involved in the CRC. These cellular processes include increased proliferative and invasive capacity, cell cycle aberration, evasion of apoptosis, enhanced EMT, promotion of angiogenesis and metastasis, and decreased sensitivity to major treatments. The miRNAs control cellular processes in CRC via regulation of pathways such as Wnt/β-catenin signaling, PTEN/AKT/mTOR axis, KRAS, TGFb signaling, VEGFR, EGFR, and P53. Hence, the goal of this review was to review miRNA biogenesis and present an updated summary of oncogenic and tumor suppressor (TS) miRNAs and their potential implication in CRC pathogenesis and responses to chemotherapy and radiotherapy. We also summarise the biological importance and clinical applications of miRNAs in the CRC., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To establish national diagnostic reference levels (NDRLs) for most common paediatric computed tomography (CT) examinations in Egypt., Methods: This was a prospective study that included all dedicated paediatric imaging centers in Egypt. Data from 1680 individual paediatric patients undergoing CT scanning of the head, chest and abdomen-pelvis were collected. Computed tomography dose indices were recorded, data were analysed and compared with the internationally published paediatric DRLs in14 countries., Results: The Egyptian NDRLs of the CTDIvol (mGy) for head, chest and abdomen-pelvis scans among four paediatric age groups were found to be (23, 27, 28, 32, 4, 5, 6, 8, 5, 6, 7, 9) mGy, respectively; and the corresponding NDRLs of the DLP (mGycm) for head, chest and abdomen-pelvis scans were found to be (345, 428, 499, 637, 67, 85, 145, 215, 97, 135, 240, 320) mGycm, respectively. There were variations in the radiation doses between CT centers and identical scanners indicating the need for dose optimization. The NDRLs of the CTDIvol (mGy) and the DLP (mGycm) values were similar to or lower than international DRLs., Conclusion: This study summarizes the results of the first Egyptian Computed Tomography survey that provides national diagnostic reference levels for paediatric patients in Egypt. Despite the reasonable NDRLs values, the study depicted certain pros and cons concerning CT practice, and identified some problems that hinder the process of optimization as well as justification in children., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. HCC initiation, progression, and therapy failure are all influenced by various variables, including microRNAs (miRNAs). miRNAs are short non-coding RNA sequences that modulate target mRNA expression by deteriorating or repressing translation. miRNAs play an imperative role in HCC pathogenesis by triggering the induction of cancer stem cells (CSCs) and their proliferation, while also delaying apoptosis, sustaining the cell cycle, and inspiring angiogenesis, invasion, and metastasis. Additionally, miRNAs modulate crucial HCC-related molecular pathways such as the p53 pathway, the Wnt/β-catenin pathway, VEGFR2, and PTEN/PI3K/AKT pathway. Consequently, the goal of this review was to give an up-to-date overview of oncogenic and tumor suppressor (TS) miRNAs, as well as their potential significance in HCC pathogenesis and treatment responses, highlighting their underpinning molecular pathways in HCC initiation and progression. Similarly, the biological importance and clinical application of miRNAs in HCC are summarized., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Prostate cancer (PC) is the third-leading cause of cancer-related deaths worldwide. Although the current treatment strategies are progressing rapidly, PC is still representing a substantial medical problem for affected patients. Several factors are involved in PC initiation, progression, and treatments failure including microRNAs (miRNAs). The miRNAs are endogenous short non-coding RNA sequence negatively regulating target mRNA expression via degradation or translation repression. miRNAs play a pivotal role in PC pathogenesis through its ability to initiate the induction of cancer stem cells (CSCs) and proliferation, as well as sustained cell cycle, evading apoptosis, invasion, angiogenesis, and metastasis. Furthermore, miRNAs regulate major molecular pathways affecting PC such as the androgen receptor (AR) pathway, p53 pathway, PTEN/PI3K/AKT pathway, and Wnt/β-catenin pathway. Furthermore, miRNAs alter PC therapeutic response towards the androgen deprivation therapy (ADT), chemotherapy and radiation therapy (RT). Thus, the understanding and profiling of the altered miRNAs expression in PC could be utilized as a non-invasive biomarker for the early diagnosis as well as for patient sub-grouping with different prognoses for individualized treatment. Accordingly, in the current review, we summarized in updated form the roles of various oncogenic and tumor suppressor (TS) miRNAs in PC, revealing their underlying molecular mechanisms in PC initiation and progression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: COVID-19 infection is a global pandemic that affected routine health services and made patients fear to consult for medical health problems, even acute abdominal pain. Subsequently, the incidence of complicated appendicitis increased during the Covid-19 pandemic. This study aimed to evaluate recurrent appendicitis after successful drainage of appendicular abscess during COVID-19., Material and Methods: A prospective cohort study conducted in the surgical emergency units of our Universities' Hospitals between March 15, 2020 to August 15, 2020 including patients who were admitted with the diagnosis of an appendicular abscess and who underwent open or radiological drainage. Main outcomes included incidence, severity, and risk factors of recurrent appendicitis in patients without interval appendectomy., Results: A total of 316 patients were included for analysis. The mean age of the patients was 37 years (SD ± 13). About two-thirds of patients were males (60.1%). More than one-third (39.6%) had co-morbidities; type 2 diabetes mellitus (T2DM) (22.5%) and hypertension (17.1%) were the most frequent. Approximately one quarter (25.6%) had confirmed COVID 19 infection. About one-third of the patients (30.4%) had recurrent appendicitis. More than half of them (56.3%) showed recurrence after three months, and 43.8% of patients showed recurrence in the first three months. The most frequent grade was grade I (63.5%). Most patients (77.1%) underwent open surgery. Age, T2DM, hypertension, COVID-19 infection and abscess size >3 cm were significantly risking predictors for recurrent appendicitis., Conclusions: Interval appendectomy is suggested to prevent 56.3% of recurrent appendicitis that occurs after 3 months. We recommend performing interval appendectomy in older age, people with diabetes, COVID-19 infected, and abscesses more than 3 cm in diameter., Research Question: Is interval appendectomy preventing a high incidence of recurrent appendicitis after successful drainage of appendicular abscess during COVID-19 pandemic?, (Copyright © 2021 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Traditionally, sheep are raised in Egypt for meat and wool production. Selection for higher wool quality could increase its suitability for particular processing procedures in the wool industry, which maximizes the profit of the sheep production enterprise. In this research, the effect of genetic polymorphisms of the keratin-associated protein 6-1 (KAP6-1) on wool traits was investigated in Barki sheep. Animals were genotyped by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP). Results identified a single nucleotide polymorphism (rs589531301, G > C) with three genotypes (GG, GC and CC) and the genotypic frequencies were 14.63, 43.82 and 41.55%, respectively. The KAP6-1 genotypes significantly ( p  > 0.05) affected greasy fleece weight (GFW; p  = 0.05), prickle factor (PF; p  = 0.02), staple length (SL; p  = 0.038), fiber diameter (FD; p  = 0.015), kemp score (KS; p  = 0.048), greasy color grade (GCG; p  = 0.037), luster grade (LS; p  = 0.048) and the greasy structure (GS; p  = 0.038). The noteworthy, animals with the CC genotype produce more wool (GFW = 1.116 kg) with longer SL (9.03 cm), finer wool (FD = 24.34 μm) and higher KS compared to other genotypes. The results of this report presented the KAP6-1 gene as a candidate gene to improve the wool production traits in the Egyptian Barki sheep and worldwide.

Background: Different procedures have been developed to improve the surgical outcome of peripheral nerve injuries. The purpose of this study was to evaluate the efficacy of wrapping the neurorrhaphy site utilizing dura substitute graft as an alternative conduit in the management of peripheral nerve injury., Methods: This retrospective clinical case series included 42 patients with a single peripheral nerve injury. The mean age was 26.8 ± 11 years, and the mean duration of symptoms was 3 ± 1.8 months. The visual analogue score (VAS) for pain and the Medical Research Council's (MRC) grading for motor power were used to evaluate the functional outcome among our patients. All patients were operated on for primary microscopic end-to-end repair, followed by wrapping the neurorrhaphy site with dura substitute graft as a conduit. Patients were followed in the outpatient clinic with regular visits for average of 6 months., Results: Thirty-seven patients (83%), showed functional improvement in all aspects, the VAS for pain and the MRC for motor power, as well as the functional state. One patient (2.3%) developed a postoperative hematoma collection, which needed immediate evacuation. Superficial wound infection, reported in two patients (4.7%), was treated conservatively. No postoperative neuroma was observed among our patients during the follow-up period., Conclusion: Wrapping the neurorrhaphy site utilizing dura substitute as conduit appears to be safe and might prove effective in managing peripheral nerve injury., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Aims: Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats., Main Methods: we prepared OLM niosomes (OLM-NIO) with different surfactant: cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30 mg/kg), OLM or OLM-NIO (10 mg/kg) for 3 days before IND (25 mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers., Key Findings: OLM-NIO prepared with span 60:cholesterol ratio (1:1) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8 nm, low polydispersity 0.229 ± 0.009, and high zeta-potential -35.3 ± 1.2 mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes., Significance: We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Tamoxifen (TAM) therapy has been associated with fatty liver diseases. Recently, multiple reports have also shown that TAM is related to cognitive impairment in patients with breast cancer. Luteolin, a natural flavonoid, has been traditionally used to treat various inflammatory disorders, such as chronic liver diseases, cognitive impairments, and cancers. This study aimed to evaluate the potential protective effects of luteolin against the cognitive defects and liver steatosis induced by TAM in rats., Experimental Approach: The diseased group was subcutaneously (s.c) injected with TAM at a dose of 1 mg/kg daily for 7 days. The cotreated groups were given luteolin via oral gavage at a dose of 20 or 40 mg/kg concomitantly with s.c injection of TAM at a dose of 1 mg/kg for 7 days. All the groups were subjected to behavioral tests 24 h after the last TAM injection. Then, the rats were sacrificed 3 days after the last TAM injection., Results: Luteolin cotreatment significantly alleviated the behavioral defects in rats with TAM-induced cognitive impairment. This finding was supported by the reversal of neurodegeneration in the cortex and in the hippocampal regions of the brain. Furthermore, luteolin attenuated hepatic steatosis and decreased the levels of serum aminotransferases and hypertriglyceridemia. As an anti-inflammatory agent, luteolin cotreatment similarly decreased the levels of hepatic inflammatory markers and increased the levels of hepatic β-catenin in TAM-induced fatty liver., Conclusions: Luteolin improved the TAM-induced cognitive impairment and hepatic steatosis in rats by alleviating inflammation and modulating hepatic β-catenin levels., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To achieve the advanced anticancer activity of nanocomposites fabricated with graphene oxide (GO), a novel procedure was used during the fabrication of chitosan (CS) or ethylene diamine tetra acetic acid (EDTA). The synthesized GO-based nanocomposites were distinguished through different analytical techniques. The cytotoxic activity was examined using MTT assays against three different cancer cell lines. Cell cycle distribution and apoptosis were studied by flow cytometry. Caspase-8, caspase-9, and VEGFR-2 levels were determined using the ELISA technique. HRTEM results revealed a regular 2D thin sheet with a transparent surface in non-modified GO and for GO-CS, the surface of GO has clear cuts and lines had developed due to CS insertion. Concerning the MCF-7 breast cancer cell line, the lowest IC 50 values were recorded, suggesting the most powerful cytotoxic effect on breast cancer cells. Treatment with GO-EDTA resulted in the lowest IC 50 value of 3.8 ± 0.18 μg mL -1 . As indicated by the annexin V-FITC apoptosis assay, the total apoptosis highest percentage was in GO-EDTA treatment (30.12%). In addition, the study of cell cycle analysis showed that GO-EDTA arrested the cell cycle primarily in the G0/G1 phase (33.74%). CS- and EDTA-conjugated GO showed an anti-cancer activity through their cytotoxic effect against the MCF-7 breast cancer cell line., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Angiogenesis is a multistep process implicated in the pathophysiology and progression of diabetic nephropathy (DN). Angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) have an important role in DN. We performed a randomized-controlled trial of lisinopril alone (an ACEI) or in combination with verapamil (a CCB) as a therapy for DN in type 2 diabetes mellitus (T2DM) patients with hypertension (HTN) and urinary albumin creatinine ratio (UACR) (30-300 mg/g) also to evaluate their effect on UACR, the angiogenic proteins: Angiopoietin 2 (Ang-2) and Endostatin (EST). Forty T2DM patients with microalbuminuria, aged 45-65 years were included. Patients were randomly assigned into group 1 receiving oral lisinopril and group 2 receiving oral lisinopril and verapamil once daily. After 3 months follow-up fasting blood glucose (FPG), HbA1c, lipid profile, UACR, serum urea and creatinine levels were assessed. EST and Ang-2 were measured using ELISA technique. Baseline Ang-2 and EST levels were elevated in both groups compared with controls (p<0.001). After follow-up, group 2 had significantly decreased FPG, HbA1c, UACR, EST and Ang-2 compared with their baseline levels (p<0.001 for all comparisons) and with group 1 (p<0.001). No adverse reactions were reported. Baseline EST and Ang-2 were positively correlated to UACR (r=0.753, p<0.001) (r=0.685, p<0.001). Lisinopril/verapamil combination enhanced glycemic control and kidney function via diminishing EST and Ang-2. This combination can be considered as a safe and effective approach for early stage nephropathy therapy in T2DM., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Terminal sterilization of bone allograft by gamma radiation is required to reduce the risk of infection. Free radical scavengers could be utilized to minimize the deteriorating effects of gamma radiation on bone allograft mechanical properties. The objective of this research is to assess the changes in structural and chemical composition induced by hydroxytyrosol (HT) and alpha lipoic acid (ALA) free radical scavengers in gamma sterilized cortical bone. Bovine femurs specimens were soaked in different concentrations of HT and ALA for 7 and 3 days respectively before irradiation with 35 KGy gamma radiation. The attenuated total reflection-Fourier transform infrared spectroscopy and the X-ray diffraction techniques were utilized to analyze the changes in chemical composition induced by irradiation in the presence of free radical scavengers. A significant increase in the proportion of amide I and amide II to phosphate was noticed in the irradiated group, while in the pretreated groups with ALA and HT this effect was minimized. In addition, gamma radiation reduced the mature to immature cross links while ALA and HT alleviated this reduction. No significant changes were noticed in the mineral crystallinity or crystal size. Bone chemical structure has been changed due to gamma irradiation and these changes are mainly relevant to amide I, amide II proportions and collagen crosslinks. The deteriorating effects of gamma sterilization dose (35 kGy) on chemical structure of bone allograft can be alleviated by using (HT) and (ALA) free radical scavengers before irradiation.

Objective: Milk production is one of the most desirable traits in livestock. Recently, the toll-like receptor (TLR) has been identified as a candidate gene for milk traits in cows. So far, there is no information concerning the contribution of this gene in milk traits in sheep. This study was designed to investigate the TLR 4 gene polymorphisms in Barki ewes in Egypt and then correlate that with milk traits in order to identify potential single nucleotide polymorphisms (SNPs) for these traits in sheep., Methods: A part of the ovine TLR 4 gene was amplified in Barki ewes, to identify the SNPs. Consequently; Barki ewes were genotyped using polymerase chain reaction-single strand conformation polymorphism protocol. These genotypes were correlated with milk traits, which were the daily milk yield (DMY), protein percentage (PP), fat percentage (FP), lactose percentage, and total solid percentage (TSP)., Results: Age and parity of the ewe had a significant effect (p<0.05 or p<0.01) on DMY, FP, and TSP. The direct sequencing identified a missense mutation located in the coding sequence of the gene (rs592076818; c.1710C>A) and was predicted to change the amino acid sequence of the resulted protein (p.Asn570Lys). The association analyses suggested a significant effect (p<0.05) of the TLR genotype on the FP and PP, while the DMY tended to be influenced as well (p = 0.07). Interestingly, the presence of the G allele tended to increase the DMY (+40.5 g/d) and significantly (p<0.05 or p<0.01) decreased the FP (-1.11%), PP (-1.21%), and TSP (-7.98%)., Conclusion: The results of this study suggested the toll-like receptor 4 (TLR4) as a candidate gene to improve milk traits in sheep worldwide, which will enhance the ability to understand the genetic architecture of genes underlying SNPs that affect such traits.

Background and Aim: Sheep productivity in developing countries is crucial, as this animal is an essential source of meat and wool. Myostatin ( MSTN ) plays an important role in the regulation of muscle mass through the regulation of muscle growth, differentiation, and regeneration. The present study sought to investigate genetic variation in the first intron of the MSTN gene and the association of variants with growth traits in major sheep breeds in Egypt (Barki, Ossimi, and Rahmani) and Saudi Arabia (Najdi) using polymerase chain reaction (PCR) and sequencing., Materials and Methods: Blood samples were collected, and DNA was extracted from 75 animals. A 386 bp fragment in the first intron of the MSTN gene was amplified using PCR. Polymorphic sites were detected using direct sequencing and then correlated with growth traits using a general linear model., Results: Sequence analysis of the first intron of MSTN gene identified six single-nucleotide polymorphisms (SNPs) in the studied breeds. Four mutual SNPs were determined: c.18 G>T, c.241 T>C, c.243 G>A, and c.259 G>T. In addition, two SNPs c.159 A>T and c.173 T>G were monomorphic (AA and TT, respectively) in the Ossimi, Rahmani, and Najdi breeds and polymorphic in the Barki breed. The association analysis revealed that the c.18 G>T and c.241 C>T significantly associated (p<0.05) with birth weight and average daily weight gain, respectively., Conclusion: Our results strongly support MSTN as a candidate gene for marker-assisted selection in sheep breeding programs. Furthermore, the identified variants may be considered as putative markers to improve growth traits in sheep., (Copyright: © Osman, et al.)

Background: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic homolog 7 (SMAD7) are important transforming growth factor-β (TGF-β) signaling antagonists, however their roles in acute myeloid leukemia (AML) remains unclear. Telomerase reverse transcriptase (TERT) may be involved in regulating BAMBI and SMAD7 expressions; a role beyond telomeres that is not clinically validated yet., Objective: In this study, we examined the expression levels and prognostic values of BAMBI, SMAD7 and TERT and their association with AML patients' outcomes., Methods: Blood samples were collected from 74 de-novo AML patients and 16 controls. Real-time quantitative PCR (qRT-PCR) was performed to analyze BAMBI, SMAD7 and TERT expressions., Results: BAMBI and SMAD7 expression in AML were significantly upregulated versus controls (p< 0.05). BAMBI, SMAD7 and TERT levels were significantly correlated together (p< 0.001). Kaplan-Meier analysis indicated that patients with high BAMBI, SMAD7 and TERT expression levels had markedly shorter event free survival (EFS) and overall survival (OS) time (p< 0.01). Furthermore, multivariate analysis revealed that only high BAMBI expression was an independent risk factor for OS (p= 0.001)., Conclusions: BAMBI is a novel biomarker in predicting prognosis in AML patients. Moreover, a potential interplay is found between BAMBI, SMAD7 and TERT in AML pathogenies.

Understanding the microbial ecology of a system allows linking members of the community and their metabolic functions to the performance of the wastewater bioreactor. This study provided a comprehensive conceptual framework for microbial communities in wastewater treatment electro-bioreactors (EBRs). The model was based on data acquired from monitoring the effect of altering different bioreactor operational parameters, such as current density and hydraulic retention time, on the microbial communities of an EBR and its nutrient removal efficiency. The model was also based on the 16S rRNA gene high-throughput sequencing data analysis and bioreactor efficiency data. The collective data clearly demonstrated that applying various electric currents affected the microbial community composition and stability and the reactor efficiency in terms of chemical oxygen demand, N and P removals. Moreover, a schematic that recommends operating conditions that are tailored to the type of wastewater that needs to be treated based on the functional microbial communities enriched at specific operating conditions was suggested. In this study, a conceptual model as a simplified representation of the behavior of microbial communities in EBRs was developed. The proposed conceptual model can be used to predict how biological treatment of wastewater in EBRs can be improved by varying several operating conditions.

Background: Catheter-related thrombosis (CRT) is a serious complication of vascular catheters. Retrograde catheter insertion has been shown to decrease pericatheter hemostasis and thrombosis, but it is technically challenging. The current in silico trial is an analytical approach to evaluating different approaches to designing retrograde flow into a vascular catheter., Methods: The novel catheter design aims to provide antistasis retrograde flow (ASRF) of fluid through multiple backward-directed side openings, with a self-closing terminal opening to facilitate standard insertion. Four different models of the catheter were evaluated by computational fluid dynamic studies, with retrograde-angled openings of 15°, 30°, 45°, and 60° to the long axis of the catheter., Results: ASRF successfully reduced the areas of fluid stagnation in models with 15° and 30° openings. Models with 45° and 60° did not significantly reduce stagnation. ASRF is reversed by the main bloodstream after a few millimeters. The novel catheter design achieved a slightly higher saline flow rate compared with the standard catheter (89.75, 91.72, 94.13, and 94.26 mL/min for 15°, 30°, 45°, and 60° designs, respectively, versus 86.93 mL/min for the standard catheter)., Conclusions: The novel ASRF vascular catheter reduces pericatheter fluid stasis and has the potential to reduce CRT. Further in vitro and in vivo trials are warranted to validate these findings and evaluate clinical efficacy.

Gamma radiation sterilization is the method used by the majority of tissue banks to reduce disease transmission from infected donors to recipients through bone allografts. However, many studies have reported that gamma radiation impairs the structural and mechanical properties of bone via formation of free radicals, the effect of which could be reduced using free radical scavengers. The aim of this study is to examine the radioprotective role of hydroxytyrosol (HT) and alpha lipoic acid (ALA) on the mechanical properties of gamma-sterilized cortical bone of bovine femur, using three-point bending and microhardness tests. Specimens of bovine femurs were soaked in ALA and HT for 3 and 7 days, respectively, before being exposed to 35-kGy gamma radiation. In unirradiated samples, both HT and ALA pre-treatment improved the cortical bone bending plastic properties (maximum bending stress, maximum bending strain, and toughness) without affecting microhardness. Irradiation resulted in a drastic reduction of the plastic properties and an increased microhardness. ALA treatment before irradiation alleviated the aforementioned reductions in maximum bending stress, maximum bending strain, and toughness. In addition, under ALA treatment, the microhardness was not increased after irradiation. For HT treatment, similar effects were found. In conclusion, the results indicate that HT and ALA can be used before irradiation to enhance the mechanical properties of gamma-sterilized bone allografts.

Objectives: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation., Data Sources: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching., Study Selection: Studies in mechanically ventilated children that compared early with late tracheostomy were included., Data Extraction: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark)., Data Synthesis: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis., Conclusions: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.