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  1. Suleman M, Faizullah, Khan A, Mohammad Sayaf A, Alghamdi A, Alghamdi SA, et al.
    Curr Med Chem, 2024 Aug 27.
    PMID: 39253929 DOI: 10.2174/0109298673311962240815055821
    BACKGROUND: Colorectal cancer (CRC) stands as the third most widespread cancer worldwide in both men and women, witnessing a concerning rise, especially in younger demographics. Abnormal activation of the Non-Receptor Tyrosine Kinase c-Src has been linked to the advancement of several human cancers, including colorectal, breast, lung, and pancreatic ones. The interaction between c-Src and Hexokinase 2 (HK2) triggers enzyme phosphorylation, significantly boosting glycolysis, and ultimately contributing to the development of CRC.

    OBJECTIVES: The objectives of this study are to examine the influence of newly identified mutations on the interaction between c-Src and the HK2 enzyme and to discover potent phytocompounds capable of disrupting this interaction.

    METHODS: In this study, we utilized molecular docking to check the effect of the identified mutation on the binding of c-Src with HK2. Virtual drug screening, MD simulation, and binding free energy were employed to identify potent drugs against the binding interface of c-Src and HK2.

    RESULTS: Among these mutations, six (W151C, L272P, A296S, A330D, R391H, and P434A) were observed to significantly disrupt the stability of the c-Src structure. Additionally, through molecular docking analysis, we demonstrated that the mutant forms of c-Src exhibited high binding affinities with HK2. The wildtype showed a docking score of -271.80 kcal/mol, while the mutants displayed scores of -280.77 kcal/mol, -369.01 kcal/mol, -324.41 kcal/mol, -362.18 kcal/mol, 266.77 kcal/mol, and -243.28 kcal/mol for W151C, L272P, A296S, A330D, R391H, and P434A respectively. Furthermore, we identified five lead phytocompounds showing strong potential to impede the binding of c-Src with HK2 enzyme, essential for colon cancer progression. These compounds exhibit robust bonding with c-Src with docking scores of -7.37 kcal/mol, -7.26 kcal/mol, -6.88 kcal/mol, -6.81 kcal/mol, and -6.73 kcal/mol. Moreover, these compounds demonstrate dynamic stability, structural compactness, and the lowest residual fluctuation during MD simulation. The binding free energies for the top five hits (-42.44±0.28 kcal/mol, -28.31±0.25 kcal/mol, -34.95±0.44 kcal/mol, -38.92±0.25 kcal/mol, and -30.34±0.27 kcal/mol), further affirm the strong interaction of these drugs with c-Src which might impede the cascade of events that drive the progression of colon cancer.

    CONCLUSION: Our findings serve as a promising foundation, paving the way for future discoveries in the fight against colorectal cancer.

  2. Majrashi MAA, Bairwan RD, Mushtaq RY, Khalil HPSA, Badr MY, Alissa M, et al.
    Int J Biol Macromol, 2024 May;266(Pt 2):131333.
    PMID: 38574916 DOI: 10.1016/j.ijbiomac.2024.131333
    This study investigates the potential of utilizing green chemically treated spent coffee grounds (SCGs) as micro biofiller reinforcement in Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) biopolymer composites. The aim is to assess the impact of varying SCG concentrations (1 %, 3 %, 5 %, and 7 %) on the functional, thermal, mechanical properties and biodegradability of the resulting composites with a PHBV matrix. The samples were produced through melt compounding using a twin-screw extruder and compression molding. The findings indicate successful dispersion and distribution of SCGs microfiller into PHBV. Chemical treatment of SCG microfiller enhanced the interfacial bonding between the SCG and PHBV, evidenced by higher water contact angles of the biopolymer composites. Field Emission Scanning Electron Microscopy (FE-SEM) confirmed the successful interaction of treated SCG microfiller, contributing to enhanced mechanical characteristics. A two-way ANOVA was conducted for statistical analysis. Mass losses observed after burying the materials in natural soil indicated that the composites degraded faster than the pure PHBV polymer suggesting that both composites are biodegradable, particularly at high levels of spent coffee grounds (SCG). Despite the possibility of agglomeration at higher concentrations, SCG incorporation resulted in improved functional properties, positioning the green biopolymer composite as a promising material for sustainable packaging and diverse applications.
  3. Yamin D, Uskoković V, Wakil AM, Goni MD, Shamsuddin SH, Mustafa FH, et al.
    Diagnostics (Basel), 2023 Oct 18;13(20).
    PMID: 37892067 DOI: 10.3390/diagnostics13203246
    Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes.
  4. Naveed M, Jabeen K, Naz R, Mughal MS, Rabaan AA, Bakhrebah MA, et al.
    Microorganisms, 2022 Aug 10;10(8).
    PMID: 36014038 DOI: 10.3390/microorganisms10081621
    Enterobacter cloacae is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.
  5. Naveed M, Hassan JU, Ahmad M, Naeem N, Mughal MS, Rabaan AA, et al.
    Medicina (Kaunas), 2022 Sep 27;58(10).
    PMID: 36295517 DOI: 10.3390/medicina58101356
    Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.
  6. Yong SJ, Halim A, Halim M, Ming LC, Goh KW, Alfaresi M, et al.
    Expert Opin Investig Drugs, 2023;32(7):655-667.
    PMID: 37534972 DOI: 10.1080/13543784.2023.2242773
    INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.

    AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.

    EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

  7. Wada Y, Ibrahim AB, Umar YA, Afolabi HA, Wada M, Alissa M, et al.
    J Infect Public Health, 2024 Apr 10;17(6):1023-1036.
    PMID: 38657438 DOI: 10.1016/j.jiph.2024.04.004
    Wild birds could be a reservoir of medically relevant microorganisms, particularly multidrug-resistant Enterococcus spp. Resistant bacteria's epidemiology and transmission between animals and humans has grown, and their zoonotic potential cannot be ignored. This is the first study to evaluate the status of vancomycin resistant enterococci (VRE) in various wild bird species using meta-analysis and a systematic review. In this study, the pooled prevalence was obtained by analyzing data from published articles on the occurrence of VRE in wild bird species. It's unclear how the antibiotic resistance gene transfer cycle affects wild birds. Google Scholar and PubMed were used to conduct the research. The data and study methodology was assessed and extracted by two reviewers independently, with a third reviewing the results. Heterogeneity between study and publication bias were analyzed using the random effect model. Thirty-eight studies were included in the meta-analysis. 382 out of the 4144 isolates tested, were VRE. The pooled prevalence of VRE among wild birds was estimated at 11.0% (95% CI; 6.9 -17.2%; I2 = 93.204%; P 
  8. Rahbeni TA, Satapathy P, Itumalla R, Marzo RR, Mugheed KAL, Khatib MN, et al.
    JMIR Public Health Surveill, 2024 Apr 30;10:e54769.
    PMID: 38687992 DOI: 10.2196/54769
    BACKGROUND: The unprecedented emergence of the COVID-19 pandemic necessitated the development and global distribution of vaccines, making the understanding of global vaccine acceptance and hesitancy crucial to overcoming barriers to vaccination and achieving widespread immunization.

    OBJECTIVE: This umbrella review synthesizes findings from systematic reviews and meta-analyses to provide insights into global perceptions on COVID-19 vaccine acceptance and hesitancy across diverse populations and regions.

    METHODS: We conducted a literature search across major databases to identify systematic reviews and meta-analysis that reported COVID-19 vaccine acceptance and hesitancy. The AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) criteria were used to assess the methodological quality of included systematic reviews. Meta-analysis was performed using STATA 17 with a random effect model. The data synthesis is presented in a table format and via a narrative.

    RESULTS: Our inclusion criteria were met by 78 meta-analyses published between 2021 and 2023. Our analysis revealed a moderate vaccine acceptance rate of 63% (95% CI 0.60%-0.67%) in the general population, with significant heterogeneity (I2 = 97.59%). Higher acceptance rates were observed among health care workers and individuals with chronic diseases, at 64% (95% CI 0.57%-0.71%) and 69% (95% CI 0.61%-0.76%), respectively. However, lower acceptance was noted among pregnant women, at 48% (95% CI 0.42%-0.53%), and parents consenting for their children, at 61.29% (95% CI 0.56%-0.67%). The pooled vaccine hesitancy rate was 32% (95% CI 0.25%-0.39%) in the general population. The quality assessment revealed 19 high-quality, 38 moderate-quality, 15 low-quality, and 6 critically low-quality meta-analyses.

    CONCLUSIONS: This review revealed the presence of vaccine hesitancy globally, emphasizing the necessity for population-specific, culturally sensitive interventions and clear, credible information dissemination to foster vaccine acceptance. The observed disparities accentuate the need for continuous research to understand evolving vaccine perceptions and to address the unique concerns and needs of diverse populations, thereby aiding in the formulation of effective and inclusive vaccination strategies.

    TRIAL REGISTRATION: PROSPERO CRD42023468363; https://tinyurl.com/2p9kv9cr.

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