Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

Platinum-based targeted chemotherapies and reversal of cisplatin resistance in non-small cell lung cancer (NSCLC).

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance.

Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

Fabrication and optimization of febuxostat-loaded chitosan nanocarriers for better pharmacokinetics profile.

The current research was planned to enhance the bioavailability of hydrophobic drug after oral administration through the development of a nanoparticle drug delivery system (DDS). Therefore, febuxostat-loaded chitosan nanoparticles (FLC NPs) were prepared using a modified ionic gelation method and optimized the reaction conditions through the design of experiments. Design expert software was used to check the desirability of the central composite design and the interactive effects of the independent variables (chitosan concentration, ratio of chitosan to linker, and pH of the medium) on the response variables (size distribution, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE)) of FLC NPs. All ingredients of the optimized formulation (formulation Q) were compatible with each other as evident from FTIR, PXRD, and TGA studies, and displayed 234.7 nm particle size, 0.158 PDI, 25.8 mV zeta potential, and 76.9 % EE. TEM, SEM, and AFM exhibited a smooth, dense, and uniform structure without any visible pores in the structure of FLC NPs. The in vitro and in vivo drug release studies described a sustained release pattern of febuxostat and increased relative bioavailability by 286.63 %. Considering these findings, this chitosan nanoparticle DDS can further be used for improving the EE and bioavailability of hydrophobic drugs.

Dual activity of indolin-2-ones containing an arylidene motif: DNA and BSA interaction.

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus. Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA (KSV = 1.35 × 104 and 3.05 × 104 M-1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced (Ka = 6.1 × 106 M-1). In summary, IND that contains m-aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector.

Polysaccharide-Based Hydrogel from Seeds of Artemisia vulgaris: Extraction Optimization by Box-Behnken Design, pH-Responsiveness, and Sustained Drug Release.

The current research work focuses on the extraction and optimization of the hydrogel (AVM) from the seeds of Artemisia vulgaris using Box-Behnken design-response surface methodology (BBD-RSM). The AVM was obtained through a hot water extraction process. The influence of different factors, including pH (U = 4 to 10), temperature (V = 25 to 110 °C), seed/water ratio, i.e., S/W ratio (W = 1/10 to 1/70 w/v), and seed/water contact time, i.e., S/W time (X = 1 to 12 h) on the yield of AVM was evaluated. The p-value for the analysis of variance (ANOVA) was found to be <0.001, indicating that the yield of AVM mainly depended on the abovementioned factors. The highest yield of AVM, i.e., 15.86%, was found at a pH of 7.12, temperature of 80.04 °C, S/W ratio of 1/33.24 w/v, and S/W time of 8.73 h according to Design-Expert Software. The study of the pH-responsive behavior of AVM in tablet form (formulation AVT3) revealed that AVM is a pH-responsive material with significantly high swelling at pH 7.4. However, less swelling was witnessed at pH 1.2. Moreover, AVM was found to be a sustained release material for esomeprazole at pH 7.4 for 12 h. The drug release from AVT3 was according to the super case-II transport mechanism and zero-order kinetics.

Synthesis, Characterization, and Biological Evaluation of Meldrum's Acid Derivatives: Dual Activity and Molecular Docking Study.

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 µM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 µM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

Antibacterial efficacy of indigenous Pakistani honey against extensively drug-resistant clinical isolates of Salmonella enterica serovar Typhi: an alternative option to combat antimicrobial resistance.

BACKGROUND: Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi. METHODS: We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method. RESULTS: All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of blaTM-1, Sul1, qnrS, gyrA, gyrB, and blaCTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7-15 mm and neem honey had a zone of inhibition of 7-12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates. CONCLUSION: Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates.

Phthalazone tethered 1,2,3-triazole conjugates: In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities.

New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; 1H, 13C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38. The antiproliferative assessment of derivatives 12-21 showed potent activity of compounds 16, 18, and 21 compared to the anticancer drug doxorubicin. Compound 16 showed selectivity (SI) towardthe tested cell lines ranging from 3.35 to 8.84 when compared to Dox., that showed SI ranged from 0.75 to 1.61. Derivatives 16, 18 and 21 were assessed towards VEGFR-2 inhibitory activity and result in that derivative 16 showed the potent activity (IC50 = 0.123 µM) in comparison with sorafenib (IC50 = 0.116 µM). Compound 16 caused an interference with the cell cycle distribution of MCF7 and increased the percentage of cells in S phase by 1.37-fold. In silico molecular docking of the effective derivatives 16, 18, and 21 against vascular endothelial growth factor receptor-2 (VEGFR-2) confirmed the formation of stable protein-ligand interactions within the pocket.

Discovery of Novel Tetramethylpyrazine Containing Chalcone Derivatives as Anti-Inflammatory Agents.

BACKGROUND: Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity. OBJECTIVE: As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed. METHODS: A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared. RESULTS: The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC50 values of 0.027 ± 0.004 µM and 0.150 ± 0.027 µM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1ß, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions. CONCLUSION: The findings showed that these novel compounds had a significant impact on antiinflammatory actions.

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a-e, 1,3,4-thiadiazole aryl urea 6a-d, and cyanothiouracil moieties 8a-d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

Covalent Organic Frameworks (COFs) as Multi-Target Multifunctional Frameworks.

Covalent organic frameworks (COFs), synthesized from organic monomers, are porous crystalline polymers. Monomers get attached through strong covalent bonds to form 2D and 3D structures. The adjustable pore size, high stability (chemical and thermal), and metal-free nature of COFs make their applications wider. This review article briefly elaborates the synthesis, types, and applications (catalysis, environmental Remediation, sensors) of COFs. Furthermore, the applications of COFs as biomaterials are comprehensively discussed. There are several reported COFs having good results in anti-cancer and anti-bacterial treatments. At the end, some newly reported COFs having anti-viral and wound healing properties are also discussed.

Synthetic Approaches and Pharmacological Attributes of Benzosuberone Skeleton.

BACKGROUND: Benzocycloheptanone is the main structural feature of numerous famous natural pharmacophores such as Colchicine and Theaflavins. It has gained popularity in the field of medicinal chemistry, attributing to its broad-spectrum effect. OBJECTIVE: Numerous research publications addressing the derivatization of the benzosuberone molecule have been published, and their biological and pharmacological features have been extensively addressed. Numerous derivatives have been discovered as lead compounds for the development of novel medications. Thus, the goal of this article is to summarize and analyze all published findings on the synthesis and biological assessment of the benzosuberone skeleton. METHODS: All main databases including SciFinder, PubMed and google scholar were used with appropriate keywords to select related reported literature, and further bibliography in related literature was also used to find linked reports. RESULTS: Synthetic routes to benzosuberone-based ring systems were identified from the literature and explained stepwise and after this, pharmacological activities of all benzosuberone derivatives are listed target-wise and a detailed structure-activity relationship is developed. CONCLUSION: The current review discusses numerous synthetic approaches for the synthesis of benzosuberone skeleton and its applications in many domains of medical chemistry. Compounds possessing the benzosuberone skeleton play an important role in the drug development process due to their wide range of biological actions such as anti-cancer, antibacterial, antifungal, antiinflammatory, and so on. The results of antibacterial screening and Structure-Activity Relationship (SAR) revealed that the compounds containing this skeleton with the piperazine and morpholine rings have antimicrobial potential when compared to the commercial antibiotic Norfloxacin. Despite extensive study to date, there is still room for the development of novel and efficient pharmacophores using the structure-based drug design technique.

A Smart Hydrogel from Salvia spinosa Seeds: pH Responsiveness, On-off Switching, Sustained Drug Release, and Transit Detection.

BACKGROUND: The use of synthetic and semi-synthetic materials in drug delivery systems has associated drawbacks like costly synthesis, toxicity, and biocompatibility issues. Therefore, there is a need to introduce novel materials to overcome such issues. Naturally occurring and water-swellable polysaccharides are advantageous in overcoming the above-mentioned issues. Therefore, we are reporting a novel hydrogel (SSH) isolated from the seeds of Salvia spinosa as a sustained release material. METHODS: SSH was explored for its pH-dependent and salt-responsive swelling before and after compression in a tablet form. Stimuli-responsive swelling and deswelling were also monitored at pH 7.4 and pH 1.2 in deionized water (DW) and normal saline and DW and ethanol. The sustained-release potential of SSH-based tablets was monitored at gastrointestinal tract (GIT) pH. The transit of SSH tablets was ascertained through an X-ray study. RESULTS: The swelling of SSH in powder and tablet form was found in the order of DW > pH 7.4 > pH 6.8 > pH 1.2. An inverse relation was found between the swelling of SSH and the concentration of the salt solution. The SSH showed stimuli-responsive swelling and de-swelling before and after compression, indicating the unaltered nature of SSH even in a closely packed form, i.e., tablets. Sustained release of theophylline (< 80%) was witnessed at pH 6.8 and 7.4 during the 12 h study following zeroorder kinetics, and radiographic images also showed 9 h retention in GIT. CONCLUSION: These investigations showed the potential of SSH as a pH-sensitive material for sustained and targeted drug delivery.

Rubella Virus Infections: A Bibliometric Analysis of the Scientific Literature from 2000 to 2021.

Rubella virus (RuV) generally causes a mild infection, but it can sometimes lead to systemic abnormalities. This study aimed to conduct a bibliometric analysis of over two decades of RuV research. Medical studies published from 2000 to 2021 were analyzed to gain insights into and identify research trends and outputs in RuV. R and VOSviewer were used to conduct a bibliometric investigation to determine the globally indexed RuV research output. The Dimensions database was searched with RuV selected as the subject, and 2500 published documents from the preceding two decades were reviewed. The number of publications on RuV has increased since 2003, reaching its peak in 2020. There were 12,072 authors and 16,769 author appearances; 88 publications were single-authored and 11,984 were multi-authored. The United States was the most influential contributor to RuV research, in terms of publications and author numbers. The number of RuV-related articles has continued to increase over the past few years due to the significant rubella burden in low-income nations. This study will aid in formulating plans and policies to control and prevent RuV infections.

Design, Synthesis, Molecular Modeling, and Anticancer Evaluation of New VEGFR-2 Inhibitors Based on the Indolin-2-One Scaffold.

A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity. The effects of the most potent inhibitor, 17a, on cell cycle, apoptosis, and expression of apoptotic markers (caspase-3&-9, BAX, and Bcl-2) were studied. Molecular modeling studies, such as docking simulations, physicochemical properties prediction, and pharmacokinetic profiling were performed. The results revealed that derivatives 5b, 10e, 10g, 15a, and 17a exhibited potent anticancer activities with IC50 values from 0.74-4.62 µM against MCF-7 cell line (sunitinib IC50 = 4.77 µM) and from 1.13-8.81 µM against HepG2 cell line (sunitinib IC50 = 2.23 µM). Furthermore, these compounds displayed potent VEGFR-2 inhibitory activities with IC50 values of 0.160, 0.358, 0.087, 0.180, and 0.078 µM, respectively (sunitinib IC50 = 0.139 µM). Cell cycle analysis demonstrated the ability of 17a to induce a cell cycle arrest of the HepG2 cells at the S phase and increase the total apoptosis by 3.5-fold. Moreover, 17a upregulated the expression levels of apoptotic markers caspase-3 and -9 by 6.9-fold and 3.7-fold, respectively. In addition, 17a increased the expression level of BAX by 2.7-fold while decreasing the expression level of Bcl-2 by 1.9-fold. The molecular docking simulations displayed enhanced binding interactions and similar placement as sunitinib inside the active pocket of VEGFR-2. The molecular modeling calculations showed that all the test compounds were in accordance with Lipinski and Veber rules for oral bioavailability and had promising drug-likeness behavior.

Bibliometric Analysis of Publications on the Omicron Variant from 2020 to 2022 in the Scopus Database Using R and VOSviewer.

Human respiratory infections caused by coronaviruses can range from mild to deadly. Although there are numerous studies on coronavirus disease 2019 (COVID-19), few have been published on its Omicron variant. In order to remedy this deficiency, this study undertook a bibliometric analysis of the publishing patterns of studies on the Omicron variant and identified hotspots. Automated transportation, environmental protection, improved healthcare, innovation in banking, and smart homes are just a few areas where machine learning has found use in tackling complicated problems. The sophisticated Scopus database was queried for papers with the term "Omicron" in the title published between January 2020 and June 2022. Microsoft Excel 365, VOSviewer, Bibliometrix, and Biblioshiny from R were used for a statistical analysis of the publications. Over the study period, 1917 relevant publications were found in the Scopus database. Viruses was the most popular in publications for Omicron variant research, with 150 papers published, while Cell was the most cited source. The bibliometric analysis determined the most productive nations, with USA leading the list with the highest number of publications (344) and the highest level of international collaboration on the Omicron variant. This study highlights scientific advances and scholarly collaboration trends and serves as a model for demonstrating global trends in Omicron variant research. It can aid policymakers and medical researchers to fully grasp the current status of research on the Omicron variant. It also provides normative data on the Omicron variant for visualization, study, and application.

The Molecular Detection of Class B and Class D Carbapenemases in Clinical Strains of Acinetobacter calcoaceticus-baumannii Complex: The High Burden of Antibiotic Resistance and the Co-Existence of Carbapenemase Genes.

The emergence of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (CRACB) in clinical environments is a significant global concern. These critical pathogens have shown resistance to a broad spectrum of antibacterial drugs, including carbapenems, mostly due to the acquisition of various ß-lactamase genes. Clinical samples (n = 1985) were collected aseptically from multiple sources and grown on blood and MacConkey agar. Isolates and antimicrobial susceptibility were confirmed with the VITEK-2 system. The modified Hodge test confirmed the CRACB phenotype, and specific PCR primers were used for the molecular identification of blaOXA and blaNDM genes. Of the 1985 samples, 1250 (62.9%) were culture-positive and 200 (43.9%) were CRACB isolates. Of these isolates, 35.4% were recovered from pus samples and 23.5% from tracheal secretions obtained from patients in intensive care units (49.3%) and medical wards (20.2%). An antibiogram indicated that 100% of the CRACB isolates were resistant to ß-lactam antibiotics and ß-lactam inhibitors, 86.5% to ciprofloxacin, and 83.5% to amikacin, while the most effective antibiotics were tigecycline and colistin. The CRACB isolates displayed resistance to eight different AWaRe classes of antibiotics. All isolates exhibited the blaOXA-51 gene, while blaOXA-23 was present in 94.5%, blaVIM in 37%, and blaNDM in 14% of the isolates. The blaOXA-51, blaOXA-23, and blaOXA-24 genes co-existed in 13 (6.5%) isolates. CRACB isolates with co-existing blaOXA-23, blaOXA-24, blaNDM, blaOXA-51 and blaVIM genes were highly prevalent in clinical samples from Pakistan. CRACB strains were highly critical pathogens and presented resistance to virtually all antibacterial drugs, except tigecycline and colistin.

Multiple Antimicrobial Resistance and Heavy Metal Tolerance of Biofilm-Producing Bacteria Isolated from Dairy and Non-Dairy Food Products.

Foodborne pathogens have acquired the ability to produce biofilms to survive in hostile environments. This study evaluated biofilm formation, antimicrobial resistance (AMR), and heavy metal tolerance of bacteria isolated from dairy and non-dairy food products. We aseptically collected and processed 200 dairy and non-dairy food specimens in peptone broth, incubated them overnight at 37 °C, and sub-cultured them on various culture media. Bacterial growth was identified with biochemical tests and API 20E and 20NE strips. The AMR of the isolates was observed against different antibacterial drug classes. Biofilm formation was detected with the crystal violet tube method. Heavy metal salts were used at concentrations of 250−1500 µg/100 mL to observe heavy metal tolerance. We isolated 180 (50.4%) bacteria from dairy and 177 (49.6%) from non-dairy food samples. The average colony-forming unit (CFU) count for dairy and non-dairy samples was 2.9 ± 0.9 log CFU/mL and 5.1 ± 0.3 log CFU/mL, respectively. Corynebacterium kutscheri (n = 74), lactobacilli (n = 73), and Staphylococcus aureus (n = 56) were the predominant Gram-positive and Shigella (n = 10) the predominant Gram-negative bacteria isolated. The correlation between biofilm formation and AMR was significant (p < 0.05) for most cephalosporins, aminoglycosides, and fluoroquinolones. Heavy metal tolerance tended to be higher in biofilm producers at different metal concentrations. The pathogens isolated from dairy and non-dairy food showed a high burden of AMR, high propensity for biofilm formation, and heavy metal tolerance, and pose an imminent threat to public health.

Emergence and dissemination of monkeypox, an intimidating global public health problem.

The monkeypox virus (MPXV) is the cause of a zoonotic infection similar to smallpox. Although it is endemic to Africa, it has recently begun to circulate in other parts of the world. In July 2022, the World Health Organization declared monkeypox an international public health emergency. This review aims to provide an overview of this neglected zoonotic pathogen. MPXV circulates as two distinct clades, the Central African and West African, with case fatality rates of 10.6% and 3.6%, respectively. The risk of infection is greater for those who work with animals or infected individuals. The virus' entry into the human body provokes both natural and acquired immunity. Although natural killer cells, CD4 + T cells, and CD8 + T cells play an essential role in eradicating MPXV, there is still a gap in the understanding of the host immune response to the virus. Currently, there are no specific therapeutic guidelines for treating monkeypox; however, some antiviral drugs such as tecovirimat and cidofovir may help to abate the severity of the disease. The use of nonpharmaceutical interventions and immunization can reduce the risk of infection. Increased surveillance and identification of monkeypox cases are crucial to understand the constantly shifting epidemiology of this resurging and intimidating disease. The present review provides a detailed perspective on the emergence and circulation of MPXV in human populations, infection risks, human immune response, disease diagnosis and prevention strategies, and future implications, and highlights the importance of the research community engaging more with this disease for an effective global response.