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Monoclonal antibodies (mAbs) are used to prevent, detect, and treat a broad spectrum of non-communicable and communicable diseases. Over the past few years, the market for mAbs has grown exponentially with an expected compound annual growth rate (CAGR) of 11.07% from 2024 (237.64 billion USD estimated at the end of 2023) to 2033 (679.03 billion USD expected by the end of 2033). Ever since the advent of hybridoma technology introduced in 1975, antibody-based therapeutics were realized using murine antibodies which further progressed into humanized and fully human antibodies, reducing the risk of immunogenicity. Some benefits of using mAbs over conventional drugs include a drastic reduction in the chances of adverse reactions, interactions between drugs, and targeting specific proteins. While antibodies are very efficient, their higher production costs impede the process of commercialization. However, their cost factor has been improved by developing biosimilar antibodies as affordable versions of therapeutic antibodies. Along with the recent advancements and innovations in antibody engineering have helped and will furtherly help to design bio-better antibodies with improved efficacy than the conventional ones. These novel mAb-based therapeutics are set to revolutionize existing drug therapies targeting a wide spectrum of diseases, thereby meeting several unmet medical needs. This review provides comprehensive insights into the current fundamental landscape of mAbs development and applications and the key factors influencing the future projections, advancement, and incorporation of such promising immunotherapeutic candidates as a confrontation approach against a wide list of diseases, with a rationalistic mentioning of any limitations facing this field. [ABSTRACT FROM AUTHOR]

Practically, AgNPs are converted to the positively charged Ag+ ions by dissolution process and will react with the negatively charged oxygen and nitrogen atoms in the vital organelles like DNA, mitochondrion, and the thiol group presented in protein structures and enzymes, which in terms interrupts the normal cell reproduction, and finally, the death of cell will occur according to the toxicity limit of (Ag+) silver ions level of each organ.

Background and Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major concern in Jordanian hospitals in terms of infection control. The purpose of this study was to identify the resistance patterns of Staphylococcus aureus strains isolated from surfaces of critical locations within the Al-Karak Governmental Hospital in 2019. Additionally, the study aimed to conduct whole-genome sequencing on the isolates. Materials and Methods: In February 2019, fourteen S. aureus strains were isolated from surfaces in critical sites in the Al-Karak Governmental Hospital. These isolates underwent antibiogram testing to determine their resistance profile. Genome sequencing using the Illumina MiSeq platform was applied to the extracted DNA from these isolates. The genomic data, including coding sequences, were analyzed to identify lineage, resistance genes, and plasmids. Results: The antibiogram results revealed that 11 of the 14 isolates were resistant to oxacillin, 6 to linezolid, and 1 to rifampicin, while none showed resistance to chloramphenicol. Eleven isolates were identified as MRSA, with a novel spa type (t4407) not previously reported in Jordan. High-quality sequencing data were obtained for only one isolate, i.e., A29, the genome showed 2,789,641 bp with a 32.7% GC content and contained 2650 coding sequences. Genomic analysis indicated the ST6 lineage, mecA gene (SCCmec type IVa(2B)), and a hybrid plasmid (pJOR_blaZ) carrying the blaZ gene for β-lactam resistance. Genomic data were deposited in NCBI (CP104989). The A29 genome closely resembled an MRSA genome isolated from a Danish hospital in 2011. The SNP analysis revealed identical antimicrobial resistance genes in these two genomes. Conclusions: This study unveils the first genomic sequence of an MRSA isolate from Jordan, marked by distinctive genotypic traits. The findings enhance our understanding of the MRSA types circulating in Jordan and the region and substantiate the phenomenon of intercontinental MRSA transmission. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurologic condition exhibiting motor dysfunction that affects old people. Marula oil (M-Oil) has been used longley in cosmetics and curing skin disorders. M-Oil is particularly stable due to its high concentration of monounsaturated fatty acids and natural antioxidants. The current study formulated M-Oil in an o/w nanoemulsion (M-NE) preparations and tested its anti-inflammatory and antioxidant actions against experimental parkinsonism. Methods: Four experimental groups of male albino mice were used and assigned as vehicle, PD, PD + M-Oil and PD + M-NE. Locomotor function was evaluated using the open field test and the cylinder test. Striatal samples were used to measure inflammatory and oxidative stress markers. Results: The results indicated poor motor performance of the mice in PD control group then, improvements were recorded after treatment with crude M-Oil or MNE. In addition, we found high expression and protein of inflammatory markers and malondialdehyde levels in PD group which were downregulated by using doses of crude M-Oil or M-NE. Hence, formulating M-Oil in form of M-NE enhanced its physical characters. Discussion: This finding was supported by enhanced biological activity of M-NE as anti-inflammatory and antioxidant agent that resulted in downregulation of the inflammatory burden and alleviation of locomotor dysfunction in experimental PD in mice. [ABSTRACT FROM AUTHOR]

Vitamin D3 is a fat-soluble prohormone that is activated inside the liver to produce 25-hydroxyvitamin D3 (calcidiol), and in the kidney to produce the fully active 1α, 25-dihydroxy vitamin D3 (calcitriol). A previous work piloted in our laboratory, resulted in a successful recovery of a local soil-promising Actinomyces hyovaginalis isolate CCASU-A11-2 capable of converting vitamin D3 into calcitriol. Despite the rising amount of research on vitamin D3 bioconversion into calcitriol, further deliberate studies on this topic can significantly contribute to the improvement of such a bioconversion process. Therefore, this work aimed to improve the bioconversion process, using the study isolate, in a 14 L laboratory fermenter (4 L fermentation medium composed of fructose (15 g/L), defatted soybean (15 g/L), NaCl (5 g/L), CaCO3 2 g/L); K2HPO4, (1 g/L) NaF (0.5 g/L) and initial of pH 7.8) where different experiments were undertaken to investigate the effect of different culture conditions on the bioconversion process. Using the 14 L laboratory fermenter, the calcitriol production was increased by about 2.5-fold (32.8 µg/100 mL) to that obtained in the shake flask (12.4 µg/100 mL). The optimal bioconversion conditions were inoculum size of 2% v/v, agitation rate of 200 rpm, aeration rate of 1 vvm, initial pH of 7.8 (uncontrolled); addition of vitamin D3 (substrate) 48 h after the start of the main culture. In conclusion, the bioconversion of vitamin D3 into calcitriol in a laboratory fermenter showed a 2.5-fold increase as compared to the shake flask level where, the important factors influencing the bioconversion process were the aeration rate, inoculum size, the timing of substrate addition, and the fixed pH of the fermentation medium. So, those factors should be critically considered for the scaling-up of the biotransformation process. Key points: Bioconversion of vitamin D into calcitriol has been performed in a 14 L laboratory fermenter using a local soil-promising Actinomyces hyovaginalis isolate CCASU-A11-2. The calcitriol production was increased by about 2.5-fold (32.8 µL/100 mL) to that obtained in the shake flask (12.4 µL/100 mL). Aeration rate, inoculum size, the timing of substrate addition, and the fixed pH were important factors influencing the bioconversion process. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The isolates were chosen based on reduced susceptibility to at least three classes of antimicrobial compounds and were initially identified using MALDI-TOF/MS, followed by polymerase chain reaction amplification of blaOXA-51-like genes. The susceptibility profiles were determined using a broth microdilution assay. Multi-, extensive-, and pan-drug resistance was shown by 34.8%, 63.0%, and 2.2% of the isolates, respectively. These were most susceptible to colistin (95.7%), amikacin, and trimethoprim/sulfamethoxazole (32.6% each), while only 26.1% of isolates were susceptible to tigecycline. In silico multi-locus sequence typing revealed 8 Pasteur and 22 Oxford sequence types (STs) including four novel STs (STOxf 2805, 2806, 2807, and 2808). The majority of the isolates belonged to Global Clone (GC) 2 (76.4%), GC5 (19.6%), GC4 (6.5%), GC9 (4.3%), and GC7 (2.2%) lineages. An extensive resistome potentially conferring resistance to the majority of the tested antimicrobials was identified in silico. Of all known carbapenem resistance genes, blaOXA-23 was carried by most of the isolates (69.6%), followed by ISAba1-amplified blaADC (56.5%), blaNDM-1 and blaGES-11 (21.7% each), and blaGES-35 (2.2%) genes. A significant correlation was found between carbapenem resistance and carO mutations, which were evident in 35 (76.0%) isolates. A lower proportion of carbapenem resistance was noted for strains possessing both blaOXA-23- and blaGES-11. Amikacin resistance was most probably mediated by armA, aac(6′)-Ib9, and aph(3′)-VI, most commonly coexisting in GC2 isolates. No mutations were found in pmrABC or lpxACD operons in the colistin-resistant isolates. Tigecycline resistance was associated with adeS (N268Y) and baeS (A436T) mutations. While the lineage-specific distribution of some genes (e.g., blaADC and blaOXA-51-like alleles) was evident, some resistance genes, such as blaOXA-23 and sul1, were found in all GCs. The data generated here highlight the contribution of five GCs in A. baumannii infections in Egypt and enable the comprehensive analysis of GC-specific resistomes, thus revealing the dissemination of the carbapenem resistance gene blaOXA-23 in isolates encompassing all GCs. [ABSTRACT FROM AUTHOR]

The rise of the highly lethal severe acute respiratory syndrome-2 (SARS-2) as corona virus 2019 (COVID-19) reminded us of the history of other pandemics that happened in the last century (Spanish flu) and stayed in the current century, which include Severe-Acute-Respiratory-Syndrome (SARS), Middle-East-Respiratory-Syndrome (MERS), Corona Virus 2019 (COVID-19). We review in this report the newest findings and data on the origin of pandemic respiratory viral diseases, reservoirs, and transmission modes. We analyzed viral adaption needed for host switch and determinants of pathogenicity, causative factors of pandemic viruses, and symptoms and clinical manifestations. After that, we concluded the host factors associated with pandemics morbidity and mortality (immune responses and immunopathology, ages, and effect of pandemics on pregnancy). Additionally, we focused on the burdens of COVID-19, non-pharmaceutical interventions (quarantine, mass gatherings, facemasks, and hygiene), and medical interventions (antiviral therapies and vaccines). Finally, we investigated the nanotechnology between COVID-19 analysis and immune system boosting (Nanoparticles (NPs), antimicrobial NPs as antivirals and immune cytokines). This review presents insights about using nanomaterials to treat COVID-19, improve the bioavailability of the abused drugs, diminish their toxicity, and improve their performance. [ABSTRACT FROM AUTHOR]

The poly(o-anisidine)/BaSO4 nanocomposites were prepared by oxidative polymerization of o-anisidine monomer with BaSO4 filler for the potential antibacterial properties of the composite materials. To achieve the optimal and tunable properties of the nanocomposites, the ratio of BaSO4 filler was changed at the rates of 1%, 3%, 5%, 7%, and 10% with respect to matrix. Different analytical techniques, i.e., FTIR and UV-visible spectroscopy, were employed for functional identification and optical absorption of the poly(o-anisidine)/BaSO4 nanocomposites. The FTIR data revealed the significant interaction between POA and BaSO4, as well as the good absorption behavior of the UV-visible spectra. The conducting properties were controllable by varying the load percentage of the BaSO4 filler. Furthermore, different bacterial strains, i.e., Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive), were used to evaluate the antibacterial activity of the POA/BaSO4 nanocomposites. The largest zones of inhibition 0.8 and 0.9 mm were reached using 7% and 10% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively. [ABSTRACT FROM AUTHOR]

Background: In pandemic COVID-19 (coronavirus disease 2019), the prognosis of patients has been determined using clinical data and CT (computed tomography) scans, but it is still unclear whether chest CT characteristics are correlated to COVID-19 severity. Aim: To explore the potential association between clinical data and 25-point CT score and investigate their predictive significance in COVID-19-positive patients at Fayoum University Hospital in Egypt. Methods: This study was conducted on 252 Egyptian COVID-19 patients at Fayoum University Hospital in Egypt. The patients were classified into two groups: a mild group (174 patients) and a severe group (78 patients). The results of clinical laboratory data, and CT scans of severe and mild patients, were collected, analyzed, and compared. Results: The severe group show high significance levels of CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, ferritin, lactate dehydrogenase (LDH), neutrophil percent, and heart rate (HR) than the mild group. Lymphopenia, hypoalbuminemia, hypocalcemia, and decreased oxygen saturation (SpO2) were the most observed abnormalities in severe COVID-19 patients. Lymphopenia, low SpO2 and albumin levels, elevated serum LDH, ferritin, urea, and CRP levels were found to be significantly correlated with severity CT score (P<0.0001). Conclusion: The clinical severity of COVID-19 and the CT score are highly correlated. Our findings indicate that the CT scoring system can help to predict COVID-19 disease outcomes and has a strong correlation with clinical laboratory testing. [ABSTRACT FROM AUTHOR]

In December 2019, a mysterious viral pneumonia first developed in Wuhan, China, resulting in a huge number of fatal cases. This pneumonia, which was named COVID-19, was attributed to a novel coronavirus, SARS-CoV-2. The emerging SARS-CoV-2 mutations pose the greatest risk to human health because they could result in an increase in the COVID-19 severity or the failure of current vaccines. One of these notable mutations is the SARS-CoV-2 Delta variant (B.1.617) that was first detected in India and has rapidly expanded to 115 countries worldwide. Consequently, in this study, we performed nextgeneration sequencing and phylogenetic analysis of SARS-CoV-2 during the third wave of the pandemic to determine the SARS-CoV-2 variants of concern (VOC) prevalence in Egypt. We observed several mutational patterns, revealing that SARS-CoV-2 evolution has expanded in Egypt with a considerable increase in the number of VOC. Therefore, the Egyptian authorities should take an appropriate approach to investigate the compatibility of already employed vaccines with this VOC and to examine the efficacy of the existing therapeutic regimen against new SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Despite the mounting global burden of antimicrobial resistance (AMR), the generation of new classes of effective antimicrobials still lags far behind. The interplay between multidrug resistance and biofilm formation in Acinetobacter baumannii has drastically narrowed the available therapeutic choices. The use of natural compounds holds promise as an alternate option for restoring the activity of existing antibiotics and attenuating virulence traits through reduced biofilm formation. This study aimed to evaluate the modulatory effect of combining cinnamic and gallic acids at ½MIC with various antibiotics against multidrug-resistant (MDR) A. baumannii clinical isolates as well as study the effect on the expression of the biofilm-associated genes (bap, csuE, ompA) via quantitative, real-time PCR. Combining cinnamic or gallic acid with imipenem, amikacin or doxycycline resulted in significant reduction of resistance (p < 0.05). On the contrary, no effect was recorded when both acids were combined with levofloxacin, and only cinnamic acid had a synergistic effect with colistin. The transcriptomic changes of biofilm-related genes in the presence of gallic acid at ½MIC were compared with untreated control samples. The fold expression values proved that gallic acid substantially down-regulated the respective genes in all five strong biofilm formers. Molecular docking studies of gallic and cinnamic acids on target genes revealed good binding affinities and verified the proposed mechanism of action. To the best of our knowledge, this is the first report on the effect of gallic acid on the expression of bap, csuE and ompA genes in A. baumannii, which may permit its use as an adjunct anti-virulence therapeutic strategy. [ABSTRACT FROM AUTHOR]