Raed Albiheyri

Akkermansia muciniphila is a next-generation probiotic linked to intestinal barrier integrity and host metabolic well-being. However, the mechanisms underlying its mucin utilization remain incompletely understood. In particular, the temporal hierarchy of enzyme deployment, the subcellular and extracellular-vesicle localization of individual mucin-degrading enzymes (MDEs), the fine substrate specificity of glycoside hydrolases toward distinct O-glycan linkages, and the strain-dependent differences in mucinolytic capacity have yet to be resolved. This review integrates genomic, biochemical, and metabolic data to show how A. muciniphila mucin-degrading enzymes (MDEs) degrade mucus, releasing nutrients that support A. muciniphila growth and fermentation (acetate and propionate) and cross-feeding by other bacteria, including butyrate producers. It also highlights that A. muciniphila exhibits a dual nature: it safely stimulates regulated mucus degradation, improves barrier integrity, and feeds beneficial microbes. In contrast, in specific experimental contexts, such as fiber-deprived or high-sugar murine models, dietary fiber shortage or metabolic stress has been associated with increased mucus degradation, a thinner mucus layer, and greater susceptibility to inflammation and pathogens. The probiotic effects of A. muciniphila against metabolic and inflammatory conditions may involve regulated mucin degradation, but benefits may also arise from mechanisms beyond active mucin degradation, including bacterial surface proteins and pasteurized preparations. Unlocking the safe therapeutic potential of this bacterium requires mapping out the spatial, temporal, and strain-specific details of these enzymes. Future research should combine multi-omics and host-interaction studies to clarify enzyme hierarchy, vesicle delivery, and context-dependent impacts.

Akkermansia muciniphila is a next-generation probiotic linked to the intestinal barrier integrity and host metabolic well-being. However, its mucin utilization mechanisms remain uncharacterized. This review integrates genomic, biochemical, and metabolic data to show how A. muciniphila mucus-degrading enzymes (MDEs) degrade mucus, releasing nutrients that drive short-chain fatty acid production. It also highlights that A. muciniphila exhibits a dual nature: it safely stimulates regulated mucus degradation, improves barrier integrity, and feeds beneficial microbes. In contrast, dietary fiber shortages or metabolic stress trigger excessive degradation, compromising the gut barrier and increasing susceptibility to inflammation and pathogens. The probiotic effects of A. muciniphila against metabolic and inflammatory issues are driven by strictly regulated MDEs. Unlocking the safe therapeutic potential of this bacterium requires mapping out the spatial, temporal, and strain-specific details of these enzymes. Future research should combine multi-omics and host-interaction studies to clarify enzyme hierarchy, vesicle delivery, and context-dependent impacts.

Browning is a process wherein white adipocytes differentiate into brown-like adipocytes. This process is one of the key signatures of overcoming obesity. Notably, several functional foods and dietary supplements can induce browning in human body. One such naturally occurring compound is dehydrozingerone (DHZ), which is known for its beneficial effects, including antioxidant properties. In this study, DHZ was evaluated for its effect on fat reduction in 3T3-L1 cells prior its consideration as a potential anti-obesity therapeutic. The results underpin that DHZ acts as a key activator of browning, as shown by increased expression of brown adipose tissue (BAT) markers such as uncoupling protein 1 (UCP1), PR/SET domain 16 (PRDM16), cell death-inducing DFFA-like effector A (CIDEA), T-box transcription factor 1 (TBX1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) . These changes in gene expression may be associated with activation of the AMP-activated protein kinase (AMPK) pathway, and potentially mediated by the browning effect of DHZ on 3T3-L1 adipocytes. Furthermore, the treatment of DHZ also increased expression of Carnitine palmitoyltransferase 1 (CPT1), acyl-CoA synthetase long-chain family member (ACSL), and Sirtuin 1 (SIRT1), suggesting enhanced fatty acid oxidation. While the expression of Srebp1 and LpI was reduced. These findings suggest that DHZ may possibly enhances thermogenesis and promote browning in white adipocytes, thereby suppressing lipogenesis. In conclusion, DHZ showed dual effects lipid metabolism, contributing to development of a brown-like phenotype. The results depict that DHZ could serve as a promising therapeutic candidate for the management of obesity. In addition, molecular docking analysis demonstrated strong binding affinity between DHZ and the target protein, further supporting its potential as a novel therapeutic agent. However, these considerations are preliminary, and further studies, including diet-induced animal model, are required to elucidate its mechanism of action.

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus, followed by Fusobacterium nucleatum, Prevotella, and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa, Prevotella scoposa, and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius, Actinomyces graevenitzii, Actinomyces odontolyticus, and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora’s constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65’s and Probio-093’s capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the binding pattern of phytochemicals from Nyctanthes arbor-tristis Linn to Ebola virus VP35, SARS-CoV-2 protease, Nipah virus glycoprotein, and chikungunya virus. Results: Virtual screening and AutoDock analysis revealed that arborside-C, beta amyrin, and beta-sitosterol exhibited a substantial binding affinity for specific viral targets. The arborside-C and beta-sitosterol molecules were shown to have binding energies of −8.65 and −9.11 kcal/mol, respectively, when interacting with the major protease. Simultaneously, the medication remdesivir exhibited a control value of −6.18 kcal/mol. The measured affinity of phytochemicals for the other investigated targets was −7.52 for beta-amyrin against Ebola and −6.33 kcal/mol for nicotiflorin against Nipah virus targets. Additional molecular dynamics simulation (MDS) conducted on the molecules with significant antiviral potential, specifically the beta-amyrin-VP35 complex showing a stable RMSD pattern, yielded encouraging outcomes. Conclusions: Arborside-C, beta-sitosterol, beta-amyrin, and nicotiflorin could be established as excellent natural antiviral compounds derived from Nyctanthes arbor-tristis Linn. The virus-suppressing phytochemicals in this plant make it a compelling target for both in vitro and in vivo research in the future.

When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE‐2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three‐fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long‐term clinical studies in a group of people who contracted SARS‐CoV‐2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low‐grade inflammation and often self‐report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid–liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.

HIRIP3 is a mammalian protein homologous to the yeast H2A.Z deposition chaperone Chz1. However, the structural basis underlying Chz’s binding preference for H2A.Z over H2A, as well as the mechanism through which Chz1 modulates histone deposition or replacement, remains enigmatic. In this study, we aimed to characterize the function of HIRIP3 and to identify its interacting partners in HeLa cells. Our findings reveal that HIRIP3 is specifically associated in vivo with H2A–H2B dimers and CK2 kinase. While bacterially expressed HIRIP3 exhibited a similar binding affinity towards H2A and H2A.Z, the associated CK2 kinase showed a notable preference for H2A phosphorylation at serine 1. The recombinant HIRIP3 physically interacted with the H2A αC helix through an extended CHZ domain and played a crucial role in depositing the canonical core histones onto naked DNA. Our results demonstrate that mammalian HIRIP3 acts as an H2A histone chaperone, assisting in its selective phosphorylation by Ck2 kinase at serine 1 and facilitating its deposition onto chromatin.

The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of −9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: −10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of −8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of −277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs.

Increasing antimicrobial resistance to the action of existing antibiotics has prompted researchers to identify new natural molecules with antimicrobial potential. In this study, a green system was developed for biosynthesizing gold nanoparticles (BAuNPs) using sage (Salvia officinalis L.) leaf extract bioconjugated with non-toxic, eco-friendly, and biodegradable chitosan, forming chitosan/gold bioconjugates (Chi/BAuNPs). Characterization of the BAuNPs and Chi/BAuNPs conjugates takes place using transmission electron microscopy (TEM), X-ray spectra, Fourier transform infrared (FT-IR) spectroscopy, and zeta potential (Z-potential). The chemical composition of S. officinalis extract was evaluated via gas chromatography/mass spectrometry (GC/MS). This study evaluated the antioxidant and antimicrobial activities of human pathogenic multidrug-resistant (MDR) and multisensitive (MS) bacterial isolates using the agar diffusion method. Chi/BAuNPs showed inhibition of the MDR strains more effectively than BAuNPs alone as compared with a positive standard antibiotic. The cytotoxicity assay revealed that the human breast adenocarcinoma cancer cells (MCF7) were more sensitive toward the toxicity of 5-Fu + BAuNPs and 5-Fu + Chi/BAuNPs composites compared to non-malignant human fibroblast cells (HFs). The study shows that BAuNPs and Chi/BAuNPs, combined with 5-FU NPs, can effectively treat cancer at concentrations where the free chemical drug (5-Fu) is ineffective, with a noted reduction in the required dosage for noticeable antitumor action.