Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine.

Cetirizine hydrochloride (CTZ), a second-generation anti-histaminic drug, has been recently explored for its effectiveness in the treatment of alopecia. Niosomes are surfactant-based nanovesicular systems that have promising applications in both topical and transdermal drug delivery. The aim of this study was to design topical CTZ niosomes for management of alopecia. Thin film hydration technique was implemented for the fabrication of CTZ niosomes. The niosomes were examined for vesicle size, surface charge, and entrapment efficiency. The optimized niosomal formulation was incorporated into a hydrogel base (HPMC) and explored for physical characteristics, ex vivo permeation, and in vivo dermato-kinetic study. The optimized CTZ-loaded niosomal formulation showed an average size of 403.4 ± 15.6 nm, zeta potential of - 12.9 ± 1.7 mV, and entrapment efficiency percentage of 52.8 ± 1.9%. Compared to plain drug solution, entrapment of CTZ within niosomes significantly prolonged in vitro drug release up to 12 h. Most importantly, ex-vivo skin deposition studies and in vivo dermato-kinetic studies verified superior skin deposition/retention of CTZ from CTZ-loaded niosomal gels, compared to plain CTZ gel. CTZ-loaded niosomal gel permitted higher drug deposition percentage (19.2 ± 1.9%) and skin retention (AUC0-10h 1124.5 ± 87.9 µg/mL.h) of CTZ, compared to 7.52 ± 0.7% and 646.2 ± 44.6 µg/mL.h for plain CTZ gel, respectively. Collectively, niosomes might represent a promising carrier for the cutaneous delivery of cetirizine for the topical management of alopecia.

Anti-Quorum Sensing and Anti-Biofilm Activity of Pelargonium × hortorum Root Extract against Pseudomonas aeruginosa: Combinatorial Effect of Catechin and Gallic Acid.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512-1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on lasI and lasR genes expression using qRT-PCR and simultaneous docking against LasR protein was explored. The combination downregulated lasI and lasR gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

Detection of TEM, AmpC, SHV, CTX-M, and MCR-1 Genes in Gram Negative Isolates of Urinary Tract Infections.

BACKGROUND: Urinary tract infection (UTI) is an infection caused by the presence and growth of microorganisms anywhere in the urinary tract. It is usually due to bacteria from the digestive tract which climb the opening of the urethra and begin to multiply to cause infection. However, UTI is more frequent in female than male, because of the short urethra, absence of prostatic secretion, and pregnancy. METHODS: This study was aimed to detect extended spectrum beta lactamase and MCR-1genes from Gram negative bacterial clinical isolates from urinary tract infections. Ninety-one urine samples were collected in this study, then cultured on CLED agar and identified by conventional biochemical methods. Modified Kirby-Bauer method was used for sensitivity testing. Genomic DNA extracted by boiling method, and multiplex PCR was conducted to amplify TEM, AmpC, MCR-1, SHV, and CTX-M genes from all Gram-negative isolates. RESULTS: The result of the susceptibility test revealed that the highest resistant rates were 73% for Ceftazidime, followed by 63%, 56%, and 55% for Ciprofloxacin, Gentamicin, and Co-trimoxazole, respectively, and 21% were resistant to Imipenem. Moreover, for the presence of resistance genes, multiplex PCR results displayed that the TEM gene was present in 34% of bacteria, AmpC gene was found in 49.4% of isolates. Also, 38.5% and 6.6% were positive for MCR-1 gene and SHV gene, respectively. All Proteus species were negative to MCR-1 and TEM genes. Fifty E. coli, 7 Klebsiella pneumonia, two Pseudomonas aeruginosa, and five Proteus species were positive for CTX-M gene and all Citrobacter spp. were negative for CTX-M gene. Eighty-nine isolates were positive for one or more ESBL genes, while two isolates were negative to all genes. CTX-M gene is predominant among uropathogenic bacteria and imipenem is the best effective antibiotic. CONCLUSIONS: This recent study proved that the result of the susceptibility test revealed that the highest resistant rate were 73% for Ceftazidime, followed by 63%, 56%, and 55% for Ciprofloxacin, Gentamicin, and Co-trimoxazole, respectively, and 21% were resistant to imipenem.

Prevalence of human immunodeficiency virus among pulmonary tuberculosis patients: A cross-sectional study.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is an endemic disease in Sudan, where it has rapidly become the major complication of human immunodeficiency virus (HIV) infection. Thus, this study aimed to determine the prevalence of HIV among TB patients and evaluate the co-infection rate. The association of HIV prevalence with gender, age, and duration of treatment as risk factors was also determined. A descriptive cross-sectional study was performed in Omdurman Abu Anga Hospital, Khartoum, Sudan, from October 2018 to March 2019. A total of 281 blood samples were obtained randomly from pulmonary TB patients. The plasma was examined for the presence of HIV antibodies using sandwich ELISA. A structured questionnaire was used during data collection. A noticeable marker for HIV immunoglobulin M/immunoglobulin G was found in 12 patients (4.3%), of which five patients (41.7%) were diagnosed as new TB cases. Moreover, the relationship between age, sex, and duration of TB treatment and the prevalence of HIV was not significantly different (P > 0.05). In conclusion, the prevalence of HIV antibodies among TB pulmonary patients is high. Therefore, all TB patients should be examined for HIV risk factors and advised to undergo HIV testing. Further studies are essential to provide more insights into the epidemiology of the co-infection to better report the double burden of HIV and TB among TB patients in Sudan.

Molecular detection of beta-lactamase blaCTX-M group 1 in Escherichia coli isolated from drinking water in Khartoum State.

This study aimed to detect the blaCTX-M group 1 in Escherichia coli (E. coli) isolated from drinking water in Khartoum State. Two hundred and eighty water samples were collected randomly from different areas, places, and sources from the state and examined for the presence of E. coli as a fecal contamination indicator. Isolation and identification of E. coli were performed using culture characteristics on different culture media and biochemical reactions. An antimicrobial sensitivity test was performed for all isolated E. coli using agar disk diffusion method. DNA was extracted by boiling method, and bacterial genomic DNA used as a template to detect blaCTX-M group 1 by PCR. Results showed 86 (30.7%) E. coli were isolated out of 280 water samples. Antimicrobial susceptibility testing revealed the highest resistant percentage was 59% for tetracycline, followed by 35% for gentamycin, while for chloramphenicol and cefotaxime was 22 and 20%, respectively. blaCTX-M group 1 was detected in about 40% of all isolates. This study concludes that drinking water in Khartoum State may be contaminated with feces and might be a possible source for transferring resistant bacteria. Thus, it may be one of the critical causes of increasing reports of antimicrobial resistance in Khartoum State.

Evaluation of Tamarix nilotica Fractions in Combating Candida albicans Infections.

OBJECTIVES: Evaluation of the antifungal properties of Tamarix nilotica fractions against Candida albicans clinical isolates. METHODS: The in vitro antifungal potential was evaluated by agar well diffusion and broth microdilution methods. The antibiofilm potential was assessed by crystal violet, scanning electron microscopy (SEM), and qRT-PCR. The in vivo antifungal activity was evaluated by determining the burden in the lung tissues of infected mice, histopathological, immunohistochemical studies, and ELISA. RESULTS: Both the dichloromethane (DCM) and ethyl acetate (EtOAc) fractions had minimum inhibitory concentration (MIC) values of 64-256 and 128-1024 µg/mL, respectively. SEM examination showed that the DCM fraction decreased the biofilm formation capacity of the treated isolates. A significant decline in biofilm gene expression was observed in 33.33% of the DCM-treated isolates. A considerable decline in the CFU/g lung count in infected mice was observed, and histopathological examinations revealed that the DCM fraction maintained the lung tissue architecture. Immunohistochemical investigations indicated that the DCM fraction significantly (p < 0.05) decreased the expression of pro-inflammatory and inflammatory cytokines (TNF-α, NF-kB, COX-2, IL-6, and IL-1ß) in the immunostained lung sections. The phytochemical profiling of DCM and EtOAc fractions was performed using Liquid chromatography-mass spectrometry (LC-ESI-MS/MS). CONCLUSION: T. nilotica DCM fraction could be a significant source of natural products with antifungal activity against C. albicans infections.

Outlining the Phytoconstituents of Greek Clover Herb Extract and Assessment of Its Effect against Foodborne Infections Caused by Salmonella typhimurium.

Owing to the spread of resistance between pathogenic bacteria, searching for novel compounds with antibacterial activity is essential. Here, we investigated the potential antibacterial activity of Greek clover or Trigonella foenum-graecum herb extract on Salmonella typhimurium clinical isolates. The chemical profile of the herb was initially determined using LC-ESI-MS/MS, which explored 36 different compounds. Interestingly, the fenugreek extract possessed antibacterial action in vitro with minimum inhibitory concentrations of 64 to 512 µg/mL. The potential mechanism of action was studied by elucidating the effect of the fenugreek extract on the membrane properties of S. typhimurium bacteria, including the inner and outer membrane permeability and membrane integrity. Remarkably, the fenugreek extract had detrimental effects on the membrane properties in 40-60% of the isolates. Moreover, the in vivo antibacterial action was studied using a gastrointestinal infection model with S. typhimurium bacteria. Interestingly, the fenugreek extract (200 mg/kg) improved the infection outcomes in the tested mice. This was represented by the noteworthy decrease (p < 0.05) in the bacterial count in the small intestine and caecum tissues. The survival rate of the fenugreek-extract-treated mice significantly increased compared to the S. typhimurium-infected group. Additionally, there was an improvement in the histological and immunohistochemical features of tumor necrosis factor-alpha. In addition, using an ELISA and qRT-PCR, there was an improvement in the proinflammatory and oxidative stress markers in the fenugreek-extract-treated group. Consequently, fenugreek extract should be investigated further on other food pathogens.

GAS5 lncRNA: A biomarker and therapeutic target in breast cancer.

Breast cancer is one of the most common causes of cancer-related mortality globally, and its aggressive phenotype results in poor treatment outcomes. Growth Arrest-Specific 5 long non-coding RNA has attracted considerable attention due to its pivotal function in apoptosis regulation and tumor aggressiveness in breast cancer. Gas5 enhances apoptosis by regulating apoptotic proteins, such as caspases and BCL2 family proteins, and the sensitivity of BCCs to chemotherapeutic agents. At the same time, low levels of GAS5 increased invasion, metastasis, and overall tumor aggressiveness. GAS5 also regulates EMT markers, critical for cancer metastasis, and influences tumor cell proliferation by regulating various signaling components. As a result, GAS5 can be restored to suppress tumor development as a possible therapeutic strategy, which might present promising prospects for a patient's treatment. Its activity levels might also be a crucial indicator and diagnostic parameter for prediction. This review highlights the significant role of GAS5 in modulating apoptosis and tumor aggressiveness in breast cancer, emphasizing its potential as a therapeutic target for breast cancer treatment and management.

Pollutants to pathogens: The role of heavy metals in modulating TGF-ß signaling and lung cancer risk.

Lung cancer is a malignant tumor that develops in the lungs due to the uncontrolled growth of aberrant cells. Heavy metals, such as arsenic, cadmium, mercury, and lead, are metallic elements characterized by their high atomic weights and densities. Anthropogenic activities, such as industrial operations and pollution, have the potential to discharge heavy metals into the environment, hence presenting hazards to ecosystems and human well-being. The TGF-ß signalling pathways have a crucial function in controlling several cellular processes, with the ability to both prevent and promote tumor growth. TGF-ß regulates cellular responses by interacting in both canonical and non-canonical signalling pathways. Research employing both in vitro and in vivo models has shown that heavy metals may trigger TGF-ß signalling via complex molecular pathways. Experiments conducted in a controlled laboratory environment show that heavy metals like cadmium and arsenic may directly bind to TGF-ß receptors, leading to alterations in their structure that enable the receptor to be phosphorylated. Activation of this route sets in motion subsequent signalling cascades, most notably the canonical Smad pathway. The development of lung cancer has been linked to heavy metals, which are ubiquitous environmental pollutants. To grasp the underlying processes, it is necessary to comprehend their molecular effect on TGF-ß pathways. With a particular emphasis on its consequences for lung cancer, this abstract delves into the complex connection between exposure to heavy metals and the stimulation of TGF-ß signalling.

Exploring the oncogenic and tumor-suppressive roles of Circ-ADAM9 in cancer.

Circular RNAs (circRNAs) constitute a recently identified category of closed continuous loop RNA transcripts, serving as a subset of competing endogenous RNAs (ceRNAs) with the capacity to modulate genes by acting as microRNA sponges. In the context of cancer growth, numerous investigations have explored the potential functions of circRNAs, revealing their diverse functions either as oncogenes, promoting cancer progression, or as tumor suppressors, mitigating disease development. Among these, circRNA ADAM9 (Circ-ADAM9) is now recognized as an important player in a variety of mechanisms, both physiological and pathological, especially in cancer. The aberrant expression of Circ-ADAM9 has been observed across multiple human malignancies, implying a significant involvement in tumorigenesis. This comprehensive review aims to synthesize recent findings elucidating the function of Circ-ADAM9 in many malignancies. Additionally, the review explores the possibility of Circ-ADAM9 as a valuable biomarker, offering insights into its prognostic, diagnostic, and therapeutic implications. By summarizing the latest discoveries in this field, the review contributes to our understanding of the multifaceted contribution of Circ-ADAM9 in tumor biology and its potential applications in clinical settings.

Dioon rzedowskii: An antioxidant, antibacterial and anticancer plant extract with multi-faceted effects on cell growth and molecular signaling.

This study investigated the antioxidant, anticancer, antibacterial properties of Dioon rzedowskii extract, which had not been previously explored. We aimed to determine the extract's effect on liver and breast cancer cell lines and on solid Ehrlich carcinoma (SEC) mouse model to investigate the underlying molecular mechanisms. Three female albino mice groups were established: a tumor control group, a group treated with 100 mg/kg of the extract (D100), and a group treated with 200 mg/kg of the extract (D200) for 16 days after tumor development. Results showed that the D. rzedowskii extract inhibited cell growth in both MCF-7 and HepG2 cells in a concentration-dependent manner. This was achieved by suppressing the cell proliferation and inducing apoptosis. The extract also improved liver, heart, and kidney functions compared to the tumor control. Furthermore, oral administration of the extract reduced tumor volume and alleviated oxidative stress in tumor tissue. The anticancer effects were associated with overexpression of p53 and Bax and downregulation of cyclin D1 expression, which was attributed to decreased phosphorylated MAPK kinases. Additionally, D. rzedowskii exhibited antibacterial activity against K. pneumoniae isolated from cancer patients. The extract inhibited bacterial growth and reduced the membrane integrity. The study suggests that D. rzedowskii has promising potential as an adjunctive therapy for cancer treatment. Further investigations are needed to explore its combined anticancer efficacy. These results emphasize the value of natural products in developing compounds with potential anticancer activity and support a paradigm shift in cancer management to improve patients' quality of life.

Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics studies.

The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔGTotal = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔGTotal = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).Communicated by Ramaswamy H. Sarma.

Non-coding RNA mediated regulation of PI3K/Akt pathway in hepatocellular carcinoma: Therapeutic perspectives.

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

Medicinal and chemosensing applications of chitosan based material: A review.

Chitosan (CTS), has emerged as a highly intriguing biopolymer with widespread applications, drawing significant attention in various fields ranging from medicinal to chemosensing. Key characteristics of chitosan include solubility, biocompatibility, biodegradability and reactivity, making it versatile in numerous sectors. Several derivatives have been documented for their diverse therapeutic properties, such as antibacterial, antifungal, anti-diabetic, anti-inflammatory, anticancer and antioxidant activities. Furthermore, these compounds serve as highly sensitive and selective chemosensor for the detection of various analytes such as heavy metal ions, anions and various other species in agricultural, environmental and biological matrixes. CTS derivatives interacting with these species and give analytical signals. In this review, we embark on an exploration of the latest advancements in CTS-based materials, emphasizing their noteworthy contributions to medicinal chemistry spanning the years from 2021 to 2023. The intrinsic biological and physiological properties of CTS make it an ideal platform for designing materials that interact seamlessly with biological systems. The review also explores the utilization of chitosan-based materials for the development of colorimetric and fluorimetric chemosensors capable of detecting metal ions, anions and various other species, contributing to advancements in environmental monitoring, healthcare diagnostics, and industrial processes.

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Circular RNAs in the KRAS pathway: Emerging players in cancer progression.

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.

Zingiberaceae-derived phytomolecules inhibit Japanese encephalitis virus RNA dependent RNA polymerase: a molecular dynamics study.

The Japanese encephalitis virus, (JEV), is a flavivirus mostly transmitted by Culex mosquitoes mostly present in Southeast Asia and the Western Pacific region. Ardeid-wading birds are the natural reservoir of JEV; nonetheless, pigs are frequently a key amplifying host during epidemics in human populations. Although more domestic animals and wildlife are JEV hosts, it is unclear how these animals fit into the ecology and epidemiology of the virus. Even though there is no specific therapy, vaccines are available to prevent this infection. However, current vaccinations do not work against every clinical isolate and can cause neurological problems in certain people. In this study, we have screened 501 phytochemical compounds from various plants from the Zingeberaceae family against the RdRp protein of JEV. Based on this, the top five compounds (IMPHY014466, IMPHY004928, IMPHY007097, IMPHY014179 and IMPHY005010) were selected based on the obtained docking scores, which was above -8.0 Kcal/mol. Further, the binding affinity of these selected ligands was also analysed using molecular interaction, and the presence of interactions like hydrogen bonds, hydrophobic bonds and polar bonds with respective active residues were identified and studied elaborately. Furthermore, the dynamic stability of the docked RdRp protein with these selected phytochemicals was studied using Molecular dynamic simulation and essential dynamics. The free energy landscape analysis also provided information about the energy transition responsible stability of the complex. The results obtained advocated phytochemical compounds from the zingeberaceae family for future experimental validation, as these compounds exhibited significant potential as JEV antagonists.Communicated by Ramaswamy H. Sarma.

Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant.

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

Genomic characterization of extended spectrum beta lactamases producing multidrug-resistant Escherichia coli clinically isolated harboring chromosomally mediated CTX-M-15 from Alkharj, KSA.

Extended Spectrum Beta Lactamases (ESBLs) are the most prevalent enzymes conferring resistance to beta-lactams encoded on plasmids and rarely in chromosomes. This genomic study aims to characterize Escherichia coli to identify antimicrobial resistance genes (ARG), virulence factors, and phylogenetic relationships among ESBL-positive and negative isolates of E. coli obtained from Al-Kharj, Riyadh region, Saudi Arabia. Three clinical isolates from urine and vaginal swabs were obtained and subjected to whole genome sequencing, minimum inhibitory concentration, and antibiotic sensitivity tests. The pathogenicity and ARG were discovered, and the raw genomic sequences were assembled and annotated. Two isolates (E5 and E15) were MDR and ESBLs producers; the sequence type (ST) for E5 was 58, while those for E15 and E21 were 106. Most of the virulence genes were detected as plasmid-mediated; E21 was identified with a hyper-virulent plasmid (pH 2332-166) carrying different virulence factors (TraJ, traT, iss, etsC, hlyF, and iron acquisition associated proteins), plasmids (IncFII, IncFIB, and IncFIA), and insertion sequences (ISEc31). While most of the antimicrobial resistance genes were chromosomally mediated, a rare chromosome insertion of qnrS1 and blaCTX-M-15 with co-occurrence of Tn2 and ISKpn19 was identified in the E5 isolate. The consistent preservation of these genetic elements on bacterial chromosomes and plasmids could enhance the spread of Multidrug-Resistant (MDR) strains across various Enterobacteriaceae Species. This poses a significant threat to the effectiveness of existing antimicrobial treatments.