Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention.

Antisense transcription, a prevalent occurrence in mammalian genomes, gives rise to natural antisense transcripts (NATs) as RNA molecules. These NATs serve as agents of diverse transcriptional and post-transcriptional regulatory mechanisms, playing crucial roles in various biological processes vital for cell function and immune response. However, when their normal functions are disrupted, they can contribute to human diseases. This comprehensive review aims to establish the molecular foundation linking NATs to the development of disorders like cancer, neurodegenerative conditions, and cardiovascular ailments. Additionally, we evaluate the potential of oligonucleotide-based therapies targeting NATs, presenting both their advantages and limitations, while also highlighting the latest advancements in this promising realm of clinical investigation.Abbreviations: NATs- Natural antisense transcripts, PRC1- Polycomb Repressive Complex 1, PRC2- Polycomb Repressive Complex 2, ADARs- Adenosine deaminases acting on RNA, BDNF-AS- Brain-derived neurotrophic factor antisense transcript, ASOs- Antisense oligonucleotides, SINEUPs- Inverted SINEB2 sequence-mediated upregulating molecules, PTBP1- Polypyrimidine tract binding protein-1, HNRNPK- heterogeneous nuclear ribonucleoprotein K, MAPT-AS1- microtubule-associated protein tau antisense 1, KCNQ1OT- (KCNQ1 opposite strand/antisense transcript 1, ERK- extracellular signal-regulated kinase 1, USP14- ubiquitin-specific protease 14, EGF- Epidermal growth factor, LSD1- Lysine Specific Demethylase 1, ANRIL- Antisense Noncoding RNA in the INK4 Locus, BWS- Beckwith-Wiedemann syndrome, VEGFA- Vascular Endothelial Growth component A.

Pathological insights into camel mastitis.

Camel is a multipurpose animal bred to produce milk, meat, and transport and serves as a financial reserve for pastoralists by playing an important role in social prestige and prosperity. Camel milk is a good substitute for human milk because of its exceptional nutritional properties. Udder infections are considered one of the main limitations to camel farming. In recent decades, the disease has been reported by numerous camel-producing countries in Africa and Asia, such as Egypt, Somalia, Sudan, Kenya, Saudi Arabia, and Iraq. The current review provides an overview of the forms of camel mastitis, which can be clinical mastitis characterized by hardening and swelling of the breast, pain on palpation, and visible changes in the colour and texture of the milk or subclinical mastitis refers to the presence of inflammation with no obvious signs and it can be detected by indirect tests such as the California mastitis test (CMT), somatic cell count (SCC), and microbiological examination. Major pathogens of camel mastitis are Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Corynebacterium bovis. Regarding the risk factors for camel mastitis, this study provides an overview of the most important risk factors such as severe tick infestation, teat injuries, hygienic milking protocols, and physiological disorders causing mastitis. The use of indirect tests and bacteriological studies as diagnostic tools and their values for detecting camel mastitis will also be reviewed. Based on the above, further epidemiological studies on camel mastitis are needed to have solid scientific data on disease transmission, pathogen characterization, other possible risk factors or diagnostic methods, and the impact of the disease on public health. Proper control strategies should be adopted through early diagnosis, treatment and by avoiding potential risk factors to get good quality milk from camels.

Bringing resistance modulation to epidemic methicillin resistant S. aureus of dairy through antibiotics coupled metallic oxide nanoparticles.

The current study probed methicillin resistant S. aureus from milk of different dairy farms along with its response to multiple antibiotics, assessment of risk factors, and response to antibiotic coupled nanoparticle. XRD of Np was confirmed as miller indices (hkl) values i.e. (101), (100), (002), (110), (012) and (013) while STEM finally revealed 40-60 nm nanorods in aggregated form. Total of 6 preparations viz a viz gentamicin (G), chloramphenicol (C), zinc oxide nanoparticle (Np), gentamicin coupled Np (GNp), chloramphenicol coupled Np (CNp), and simultaneously coupling of gentamicin and chloramphenicol on Np (GCNp) were formulated for their potential to bring resistance modulation. Data analysis of this study revealed 24.59% MRSA from dairy milk appearing potentially associated (OR> 1, p < 0.05) with most of assumed risk factors. MRSA in response to various antibiotics showed highest resistance against amoxicillin (100%), penicillin (100%), vancomycin (100%), and linezolid (90%). Zone of inhibitions were increased by 249.76% (GNp), 184.86% (CNp), and 279.76% (GCNp) in case of coupled preparations. Significant reduced minimum inhibitory concentration was observed in case of GCNp (7.8125 ± 0.00 µg/mL) followed by GNp (15.00 ± 0.00 µg/mL) and CNp (41.67 ± 18.042 µg/mL) as compared to Np alone (125.00 ± 0.00 µg/mL). Minimum bactericidal concentrations for GCNp, GNp, and CNp, and Np were 31.125, 62.5, 125, and 500 µg/mL, respectively. The study thus concluded increased prevalence of MRSA while coupling of ZnO nanoparticles with antibiotics significantly brought resistance modulation to MRSA.

Antimicrobial resistance modulation of MDR E. coli by antibiotic coated ZnO nanoparticles.

We evaluated three types of total six preparations against multidrug resistant E. coli i) three antibiotic coated ZnO nanoparticles (gentamicin coated nanoparticle-GNp; chloramphenicol coated nanoparticles-CNp; and both gentamicin & chloramphenicol coated nanoparticle-GCNp), ii) ZnO nanoparticle alone-Np, and iii) two antibiotics used in single (Gentamicin-G; and Chloramphenicol-C). A total of n = 200 sub-clinically positive mastitic milk samples of bovine origin were processed for isolation of MDR E. coli using microbiological and clinical laboratory & standard institute's protocols. ZnO Nps were prepared from zinc acetate dihydrate (Zn (CH3COO)2. 2H2O), polyethylene glycol (C2nH4n+2On+1), and urea (CH4N2O) by standard chemical protocol. Nps were characterized by XRD and STEM analyses while coating of antibiotics on Nps was confirmed by UV-Visible spectrophotometric analysis. Analysis of variance and student t-test were applied at 5% probability using SPSS version 22 statistical software for inferences on obtained data. There was significantly (p < 0.05) lowest minimum inhibitory concentrations (MICs) and highest zone of inhibitions (ZOIs) in case of GCNp (10.42 ± 4.51 µg/mL & 22.00 ± 1.00 mm) followed by GNp (20.79 ± 8.95 µg/mL & 20.00 ± 1.00 mm) and then CNp (25.96 ± 8.95 µg/mL & 12.33 ± 0.57 mm). Percentage increase in ZOI were expressed as 135.8, 78.43, and 312.76% by GCNp when compared with that of G, C, and Np, respectively. GNp and CNp coated preparations exhibited 114.36 and 275.73% increase in ZOI than to that of G and C, respectively. Similar trend was found in percentage reduction of MICs of preparations. Highest filamentation, indicator of bacterial damage, of E. coli was noted at MIC of GCNp followed by GNp and CNp. The study concluded antibiotic coated ZnO nanoparticles significant candidates modulating antibiotic resistance in MDR E. coli.