Emerging Insights: miRNA Modulation of Ferroptosis Pathways in Lung Cancer.

The newly discovered programmed iron-dependent necrosis, ferroptosis, is a novel pathway that is controlled by iron-dependent lipid peroxidation and cellular redox changes. It can be triggered intrinsically by low antioxidant enzyme activity or extrinsically by blocking amino acid transporters or activating iron transporters. The induction of ferroptosis involves the activation of specific proteins, suppression of transporters, and increased endoplasmic reticulum (ER) stress (a condition in which the ER, a crucial organelle involved in protein folding and processing, becomes overwhelmed by an accumulation of misfolded or unfolded proteins. This situation disrupts the normal functioning of the ER, leading to a cellular stress response known as the unfolded protein response), leading to lipid peroxidation byproduct accumulation and toxic reactive oxygen species (ROS), which are highly reactive molecules derived from diatomic oxygen and include various forms such as superoxide (O2⁻), hydroxyl radicals (•OH), and hydrogen peroxide (H2O2). Ferroptosis is closely associated with signaling molecules in lung cancer, including epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1-alpha (HIF-1α), and P53, and is regulated by epigenetic factors such as microRNAs (miRNAs). miRNAs are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Several miRNAs have been found to modulate ferroptosis by targeting key genes involved in iron metabolism, lipid peroxidation, and antioxidant defense pathways. The research on ferroptosis has expanded to target its role in lung cancer treatment and resistance prevention. This review encapsulates the significance of ferroptosis in lung cancer. Understanding the mechanisms and implications of ferroptosis in lung cancer cells may lead to targeted therapies exploiting cancer cell vulnerabilities to ferroptosis Also, improving treatment outcomes, and overcoming resistance.

The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential.

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.

LncRNAs orchestration of gastric cancer - particular emphasis on the etiology, diagnosis, and treatment resistance.

Gastric cancer (GC) remains a major public health challenge worldwide. Long non-coding RNAs (lncRNAs) play important roles in the development, progression, and resistance to the treatment of GC, as shown by recent developments in molecular characterization. Still, an in-depth investigation of the lncRNA landscape in GC is absent. However, The objective of this systematic review is to evaluate our present understanding of the role that lncRNA dysregulation plays in the etiology of GC and treatment resistance, with a focus on the underlying mechanisms and clinical implications. Research that described the functions of lncRNA in angiogenesis, stemness, epigenetics, metastasis, apoptosis, development, and resistance to key treatments was given priority. In GC, it has been discovered that a large number of lncRNAs, including MALAT1, HOTAIR, H19, and ANRIL, are aberrantly expressed and are connected with disease-related outcomes. Through various methods such as chromatin remodeling, signal transduction pathways, and microRNA sponging, they modulate hallmark cancer capabilities. Through the activation of stemness programs, epithelial-mesenchymal transition (EMT), and survival signaling, LncRNAs also control resistance to immunotherapy, chemotherapy, and targeted therapies. By clarifying their molecular roles further, we may be able to identify new treatment targets and ways to overcome resistance. This article aims to explore the interplay between lncRNAs, and GC. Specifically, the focus is on understanding how lncRNAs contribute to the etiology of GC and influence treatment resistance in patients with this disease.

GC-MS analysis and nutra-pharmaceutical potential of Mentha piperita essential oil extracted by supercritical fluid extraction and hydro-distillation.

This study reports the comparative evaluation of yield, physico-chemical composition and biological attributes (antioxidant activity, antimicrobial activity, biofilm inhibition and hemolytic activity) of peppermint (Mentha piperita L.) essential oil (EO) obtained by hydro-distillation (HD) and supercritical fluid (CO2) extraction (SCFE) methods. The yield (%) of EO obtained by HD (0.20 %) was significantly (p < 0.05) higher than that of SCFE (0.13 %) while the variation in the physical parameters like solubility, color, density (at 25 °C) and refractive index (at 25 °C) was not significant between the tested oils. The data of chemical compositional analysis revealed that menthol was the key component in the EO obtained by HD (52.85 %) and SCFE (45.51 %), followed by menthone [HD (25.93 %) and SCFE (27.3 %)] and eucalyptol [HD (8.59 %); SCFE (8.92 %)]. The EO extracted with supercritical fluid (SCFE-EO) exhibited superior (p < 0.05) DPPH free radical inhibition potential (52 %) with an IC50 value of 15.65 µg/mL and reducing power compared to that of HD-EO. The highest antimicrobial activity was exhibited by SCFE-EO against Pasturella multocida with an inhibition zone of 18.00 mm (MIC value of 86 µg/mL). The results of biofilm inhibition and hemolytic activity revealed that the SCFE method was superior to recover high quality EO in comparison to the HD method. The peppermint EO obtained by SCFE, owing to potent bioactive components, can be a potential candidate to develop nutra-pharmaceuticals.

Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance.

Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management.

The miRNA Landscape in Crohn's disease: Implications for novel therapeutic approaches and interactions with Existing therapies.

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.

Unraveling the influence of LncRNA in gastric cancer pathogenesis: a comprehensive review focus on signaling pathways interplay.

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/ß-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.

Approaches based on miRNAs in Behçet's Disease: Unveiling pathogenic mechanisms, diagnostic strategies, and therapeutic applications.

Behçet's Disease (BD) is an intricate medical puzzle, captivating researchers with its enigmatic pathogenesis. This complex ailment, distinguished by recurrent mouth and genital lesions, eye irritation, and skin injuries, presents a substantial obstacle to therapeutic research. This review explores the complex interaction of microRNAs (miRNAs) with BD, highlighting their crucial involvement in the disease's pathophysiology. miRNAs, recognized for regulatory influence in diverse biological processes, hold a pivotal position in the molecular mechanisms of autoimmune diseases, such as BD. The exploration begins with examining miRNA biogenic pathways and functions, establishing a foundational understanding of their regulatory mechanisms. Shifting to the molecular landscape governing BD, the review highlights miRNA-mediated impacts on critical signaling pathways like Notch, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protein kinase B (AKT)/mammalian target of rapamycin (mTOR), offering insights into intricate pathophysiological mechanisms. Dissecting the immunological landscape reveals the profound influence of miRNAs on BD, shedding light on the intricate modulation of immune responses and offering novel perspectives on disease etiology and progression. Beyond molecular intricacies, the review explores the clinical relevance of miRNAs in BD, emphasizing their potential as diagnostic and prognostic indicators. The discussion extends to the promising realm of miRNA-based therapeutic interventions, highlighting their potential in alleviating symptoms and altering disease progression. This comprehensive review, serving as a valuable resource for researchers, clinicians, and stakeholders, aims to decipher the intricate molecular tapestry of BD and explore the therapeutic potential of miRNAs.

Psoralen Isolated from the Roots of Dorstenia psilurus Welw. Modulate Th1/Th2 Cytokines and Inflammatory Enzymes in LPS-Stimulated RAW 264.7 Macrophages.

Dorstenia psilurus is a widely used plant spice in traditional African medicine to treat pain-related conditions. However, the anti-inflammatory mechanisms underlying this activity and the main active ingredients of D. psilurus have not yet been fully characterized. This study aimed to isolate and identify the main active anti-inflammatory constituents of the D. psilurus extract and to investigate the underlying anti-inflammatory mechanisms in murine macrophages. Chromatographic techniques and spectroscopic data were used for compound isolation and structure elucidation. The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and 15-lipoxygenase activity, respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit, and Th1/Th2 cytokine measurement was performed using a flow cytometer. The results indicated that the extract and fractions of D. psilurus inhibit NO production and proliferation of RAW 264.7 macrophage cells. Bioguided fractionation led to the identification of psoralen, a furocoumarin, as the main bioactive anti-inflammatory compound. Psoralen inhibited NO production and 15-lipoxygenase activity and reduced pro-inflammatory Th1 cytokines (IFN-γ, TNF-α, and IL-2) while increasing the secretion of anti-inflammatory cytokines (IL-4, IL-6, and IL-10) in activated RAW 264.7 macrophage cells. The encouraging results obtained in this study suggest that psoralen-based multiple modulation strategies could be a useful approach to address the treatment of inflammatory diseases.

Morphological and molecular characterization of Eimeria magna infecting local rabbit (Oryctolagus cuniculus) in Alkarg City, Saudi Arabia.

Coccidiosis is one of the most prevalent diseases found in local rabbits (Oryctolagus cuniculus), which is caused by the Eimeria. The study aimed to more reliably identify Eimeria species (Eimeria magna) infecting Local Rabbits in Alkarg City, Saudi Arabia, based the method on the molecular properties and morphological and molecular biological techniques. Sub-spheroidal oocysts measuring 21-27 × 12-16 (24 × 14.4) µm (20 n) and with a length/width (L/W) ratio of 0.9-1.1 (1.0) were identified by microscopic analysis of a fecal sample. Oocysts feature a bi-layered wall that is 1.0-1.2 (1.1) µm thick. About two-thirds of the wall's thickness is made up of a smooth outer layer. A polar granule is present, but neither a micropyle nor an oocyst residuum is present. The ovoidal sporozoites measure 15-18 × 8-11 (16.5 × 9.5) µm, have an L/W ratio of 1.6-1.8 (1.7), and take up around 21% of the oocyst's total surface. The mean size of the sub-Stieda body is 1.4 × 2.3 µm, while the average size of the Stieda body is 0.9 × 1.8 µm. The para-Stieda body is lacking. Sporocyst residuum appears membrane-bound and has an uneven form made up of several granules. With two refractile bodies below the striations and pronounced striations at the more pointed end, sporozoites are vermiform, measuring an average of 11.6 × 4.0 µm. The results of the sequencing for the 18S rDNA gene confirmed the species of Eimeria parasites found in the host (rabbits). The current parasite species is closely related to the previously described and deposited E. magna and deeply embedded in the genus Eimeria (family Eimeriidae). According to the findings, single oocyst molecular identification of Eimeria may be accomplished through consistent use of the morphological and molecular results. It is possible to draw the conclusion that the current research supplies relevant facts that help assess the potential infection and future control measures against rabbit coccidiosis to reduce the financial losses that can be incurred by the rabbit industry in Saudi Arabia.

Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/ß-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Naturally occurring benzophenones and xanthones from Garcinia smeathmannii (Planch. & Triana) Oliv. displayed anti-inflammatory effects by modulating the activities of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

DNA barcoding reveals cryptic species in the sea slater Ligia italica (Crustacea, Isopoda) from Tunisia.

Barcoding studies have provided significant insights into phylogenetic relationships among species belonging to the genus Ligia (Crustacea, Isopoda). Herein the diversity of the Italian sea slater Ligia italica from Tunisia is studied for the first time. Samples were collected from 18 localities in Tunisia, and the analysis included previously published sequences from Italy and Greece available in GenBank. Bayesian and Maximum Likelihood phylogenetic analyses were carried out using a fragment of the mitochondrial COI gene. Putative cryptic species were explored using the 'barcode gap' approach in the software ASAP. A genetic landscape shape analysis was carried out using the program Alleles in Space. The analyses revealed highly divergent and well-supported clades of L. italica dispersed across Tunisia (Clades A1 and A2), Greece (Clade B) and Italy (Clades C1 and C2). High genetic dissimilarity among clades suggested that L. italica constitute a cryptic species complex. Divergence among different L. italica lineages (Clades A, B and C) occurred around 7-4.5 Ma. The detected high genetic distances among clades did not result from atypical mitochondrial DNAs or intracellular infection by Wolbachia bacteria. The complex history of the Mediterranean Sea appears to have played a significant role in shaping the phylogeographic pattern of Ligia italica. Additional morphological and molecular studies are needed to confirm the existence of cryptic species in Ligia italica in Mediterranean.

Hedgehog signaling mastery: R51211's promise in augmenting the therapeutic efficacy of sorafenib.

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.

Unraveling the miRNA Puzzle in Atherosclerosis: Revolutionizing Diagnosis, Prognosis, and Therapeutic Approaches.

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.

Morphology, morphometry, and phylogeny of the protozoan parasite, Eimeria labbeana-like (Apicomplexa, Eimeriidae), infecting Columba livia domestica.

Introduction: Eimeria spp. are intracellular protozoan parasites of the phylum Apicomplexa causing economic losses to various wild and domestic animals. An eimerian species infecting Columba livia domestica was identified in this study. Methods: A total of 15 faecal samples were examined by floatation technique, a prevalence rate of 60% was reported. Eimerian oocysts were sporulated in 2.5% potassium dichromate solution then identified using morphological and molecular (DNA amplification of the 18S rRNA and ITS-1 genes) diagnostic techniques. Results: Sporulated oocysts were identified as Eimeria labbeana-like, after morphometry with typical bi-layered wall with spherical to subspherical oocysts morphology. A polar granule is present, but no micropyle or oocyst residuum. Sporocysts are elongated ovoidal with stieda body. Sporocyst residuum with many granules and sporozoites with refractile bodies and nucleus. Both 18S rRNA and ITS-1 sequences have been deposited in GenBank database. DNA sequences from the partial 18S rRNA generated from the oocysts were found to be related to eimerian and isosporan parasites found in domestic pigeons. For the first time, ITS-1 sequences for E. labbeana-like were provided. Conclusion: The necessity of using molecular techniques to describe pigeon intestinal coccidian parasites in conjunction with traditional morphology-based tools was emphasized in this work in order to understand the biology of such parasites.

Deployment of COVID-19 vaccine in the WHO Eastern Mediterranean Region 2021-23: How do we switch to a life course approach?

In 2020-2021, all countries of the WHO Eastern Mediterranean Region [EMR] introduced COVID-19 vaccine with inequalities in coverage across countries. As for 2023, we reviewed subsequent progress in deployment, coverage, acceptance, and integration. As of 31 December 2023, coverage in EMR reached 51% for primary series and 19 % for the first booster, higher in high income countries (77 % and 44 %, respectively) than in upper middle-income countries (49 % and 20 %), Advance Market Commitment [AMC] non-Gavi eligible countries (47 % and 15 %) and AMC Gavi eligible countries (49 % and 16 %). Thirteen countries measured coverage among healthcare workers (76 % and 43 %, respectively) and 15 among elderly (69 % and 38 %, respectively). Three rounds of the regional Knowledge, Attitudes, and Practices [KAP] survey on COVID-19 vaccine acceptance in 2021-2022 indicated that acceptance increased from 20 % in June-July 2021 to 62 % in October-November 2021, and 77 % in June-July 2022. Those unvaccinated but intending to be vaccinated decreased from 60 % to 23 % and 11 %, respectively. Unvaccinated without intention to be vaccinated decreased from 15 % to 10 % and 11 %, respectively. Twenty out of 22 countries in the region had completely or partially integrated COVID-19 vaccination into the Expanded Programme on Immunization [EPI] and Primary Health Care [PHC]. Overall, challenges to reach high-risk groups persisted as the population was less concerned about Omicron variant of the SARS-CoV-2 virus. Countries should build on the trust, momentum, and lesson-learned generated from COVID-19 vaccination to get the highest risk groups vaccinated and switch from a time bound and project type approach to a sustainable and long-term approach for COVID-19 vaccine delivery that would be integrated into the routine EPI and PHC.

Efficient drug delivery potential and antimicrobial activity of biocompatible hydrogels of dextrin/Na-alginate/PVA.

Ceftriaxone sodium belongs to the third-generation cephalosporin group and is used intramuscular and intravenous route as a broad-spectrum antibiotic. This research aims to prepare biocompatible hydrogels for targeted delivery of ceftriaxone sodium by parental route. Different proportions of polymers (natural and synthetic) in the presence of cross-linker were synthesized by solvent casting method. Ceftriaxone sodium was loaded in hydrogels in different concentrations and its drug release behavior was evaluated along with swelling and biodegradation analysis. The characterization of hydrogel was done by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) to analyze surface morphology and functional groups involved in the formation of dextrin/Na-alginate/PVA hydrogels loaded with the drug. Thermogravimetric analysis (TGA) was confirmed by thermal stability and degradation pattern of loaded and unloaded hydrogels. The drug-loaded samples presented promising antimicrobial activity against S. aureus and P. multocida and their cytotoxic nature was also studied. Drug release analysis using simulated intestinal fluid (SIF) and phosphate buffer saline(PBS) for the circulatory system shows the consistent release of the drug. The findings unveiled the development of a biocompatible and innovative hydrogel, which has potential advantages for biomedical application, particularly in enhancing the therapeutic efficacy of ceftriaxone sodium drug.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

A novel combination therapy targets sonic hedgehog signaling by the dual inhibition of HMG-CoA reductase and HSP90 in rats with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.