This study evaluated the effects of Pediococcus pentosaceus GT001 on Salmonella typhimurium (S. typhimurium)-challenged broiler chickens. Two hundred Ross 708 broiler day-old chicks with comparable weight were distributed at random into four treatments with five replicates and ten chicks per replicate. The following were the treatment groups: (B) basal diet (control); (B + S) basal diet and birds were challenged with S. typhimurium at 1.0 × 107 cfu/g; (B + P) basal diet + Pediococcus pentosaceus GT001 at 4.0 × 108 cfu/g; (B + P + S) basal diet + P. pentosaceus GT001 at 4.0 × 108 cfu/g and birds were challenged with S. typhimurium at 1.0 × 107 cfu/g. There was a significant reduction (p < 0.05) in the body weight of the Salmonella-infected birds compared to the other treatment groups. However, the FCRs of the broilers were comparable among the different treatment groups (p > 0.05). The lipid profile and liver function indices measured were significantly enhanced in the P. pentosaceus GT001-supplemented groups (B + P and B + P + S) compared to the group that was Salmonella-challenged (p < 0.05) but were similar to those in the control group. The serum antioxidant activities, such as the T-AOC, SOD, CAT, GHS-Px and MDA, were significantly improved in the P. pentosaceus GT001-supplemented groups (B + P and B + P + S) (p < 0.05). The MDA was similar in the B + P and B + P + S groups, but both were significantly lower than the control and the Salmonella groups. The administration of P. pentosaceus GT001 enhanced the lipase and amylase levels in both the serum and intestine of the broilers (p < 0.05). The immunoglobin (IgA, IgG, IgM) and cytokine (IL-10 and IL-6) levels in the serum were significantly higher in the B, B + P and B + P + S treatment groups (p < 0.05). The immune-related organs (bursa and spleen) were significantly influenced in the birds fed with P. pentosaceus GT001. No significant variation was noted among all the dietary treatments in terms of the measured meat quality indices. The small intestinal digesta content of the Salmonella load was below a detectable range after 14 days of infection (p < 0.05). No significant differences were observed among the different treatment groups in terms of the breast pH, drip loss and meat color (p > 0.05). The inclusion of P. pentosaceus GT001 also modified the community structure in the cecum. This indicates that it has health benefits and could be incorporated in the broiler diet.
Background: The Vi-diphtheria toxoid typhoid conjugate vaccine (Vi-DT) has shown promising results in preventing typhoid fever in children under 2 years of age. However, a thorough assessment of its safety and immunogenicity is required to inform vaccination strategies. This systematic review and meta-analysis aimed to determine the safety and immunogenicity of Vi-DT in children below 2 years. Methods: We systematically searched multiple databases, including PubMed, Web of Science, and Scopus, for relevant studies published up to September 2023. We included studies reporting on the safety and immunogenicity outcomes of Vi-DT compared to the control or Vi-tetanus toxoid conjugated vaccine (Vi-TT) in children below 2 years. We applied a random-effects model for meta-analysis using RevMan 5.4. We expressed the results as risk ratio (RR) with a 95% confidence interval (95%CI). Results: In this analysis, five studies were selected, encompassing 1,292 children under 2 years who received the Vi-DT vaccine. No significant difference in immediate reactions was observed within 30 min post-vaccination between Vi-DT and control groups (RR: 0.99 [95% CI: 0.19, 5.26]), nor between Vi-DT and Vi-TT groups. For solicited adverse events within 4 weeks, the VI-DT group showed no significant increase in adverse events compared to control (RR: 0.93 [95% CI: 0.78, 1.12]) or Vi-TT (RR: 0.86 [95% CI: 0.69, 1.07]). Similarly, within 7 days post-vaccination, risk ratios indicated no significant differences in adverse events between the groups. The 4-week seroconversion rate was significantly higher in the Vi-DT group compared to the control (RR: 1.99 [95% CI: 1.07, 3.69]), but no difference was found between Vi-DT and Vi-TT. Adverse events associated with typhoid conjugate vaccines were predominantly non-serious, including fever and injection site reactions. Serious adverse events were rare but included conditions like pneumonia and gastroenteritis. Conclusion: This meta-analysis highlights Vi-DT safety and immunogenicity in six to 24-month-old children. The findings support the use of this Vi-DT to expand typhoid vaccination in endemic regions, in line with WHO's strategy.
The substantial release of NH3 during composting leads to nitrogen (N) losses and poses environmental hazards. Additives can mitigate nitrogen loss by adsorbing NH3/NH4, adjusting pH, and enhancing nitrification, thereby improving compost quality. Herein, we assessed the effects of combining bacterial inoculants (BI) (1.5%) with tricalcium phosphate (CA) (2.5%) on N retention, organic N conversion, bacterial biomass, functional genes, network patterns, and enzyme activity during kitchen waste (KW) composting. Results revealed that adding of 1.5%/2.5% (BI + CA) significantly (p < 0.05) improved ecological parameters, including pH (7.82), electrical conductivity (3.49 mS/cm), and N retention during composting. The bacterial network properties of CA (265 node) and BI + CA (341 node) exhibited a substantial niche overlap compared to CK (210 node). Additionally, treatments increased organic N and total N (TN) content while reducing NH4+-N by 65.42% (CA) and 77.56% (BI + CA) compared to the control (33%). The treatments, particularly BI + CA, significantly (p < 0.05) increased amino acid N, hydrolyzable unknown N (HUN), and amide N, while amino sugar N decreased due to bacterial consumption. Network analysis revealed that the combination expanded the core bacterial nodes and edges involved in organic N transformation. Key genes facilitating nitrogen mediation included nitrate reductase (nasC and nirA), nitrogenase (nifK and nifD), and hydroxylamine oxidase (hao). The structural equation model suggested that combined application (CA) and microbial inoculants enhance enzyme activity and bacterial interactions during composting, thereby improving nitrogen conversion and increasing the nutrient content of compost products.
Agricultural Inoculants , Calcium Phosphates , Composting , Soil/chemistry , Manure , Bacteria/genetics , Nitrogen/analysis
The pollution and harm of food waste (FW) are increasingly concerned, which has the dual attributes of pollutants and resources. This study aimed to improve the synthesis efficiency of FW humic substances (HS), and investigating the effect of catechol on the formation mechanism and structure of humic acid (HA) and fulvic acid (FA). Results indicated that catechol incorporation could enable to exhibit higher HS yield and more complex structure, especially the maximum particle size of FA reached 4800 nm. This was due to the combination of catechol with multiple nitrogenous compounds, which accelerated molecular condensation. Spectroscopic scans analysis revealed that Maillard reaction occurs first. Subsequently, Maillard reaction products and amino acids were combined with different sites of catechol, which leads to the difference of molecular structure of HS. The structure of FA is characterized by an abundance of carboxyl and hydroxyl groups, whereas HA is rich in benzene and heterocyclic structures. The structural difference was responsible for the disparity in the functional properties of FA and HA. Specifically, the presence of amino, hydroxyl, pyridine, and carboxyl groups in FA contributes significantly to its chelating activity. This research provides an efficient and sustainable unique solution for the high-value of FW conversion, and provides evidence for understanding the structural evolution of HA and FA.
Refuse Disposal , Soil , Soil/chemistry , Food Loss and Waste , Maillard Reaction , Food , Polymerization , Refuse Disposal/methods , Humic Substances/analysis , Catechols , Benzopyrans/chemistry
OBJECTIVE: To study the possibility of using pediatric endocrowns to restore the second primary molar using three-dimensional (3D) finite element analysis. DESIGN: A 3D finite element model was built for a pediatric mandibular molar, starting with laser scanning a naturally extracted tooth. The access cavity had an elliptic shape with 6 mm width, 4 mm height, and 2 mm depth with a wall taper angle of 5 degrees.Two materials (Zr and E-max) were tested for the endocrown and two cementing materials (glass ionomer and resin cement) with 20 to 40 µm thickness. Twelve case studies were reported within this research as the applied load of 330 N was tested with three angulations vertical, oblique at 45 degrees, and laterally. RESULTS: Twelve linear static stress analyses were performed. The resultant stresses and deformations' distribution patterns did not alter much, and values were within the threshold of physiological tolerance. Deformations were negligibly changed with changing endocrown and cement materials. In contrast, endocrown stresses indicated zirconia endocrown would have a long lifetime, while E-max one will have a relatively short lifetime. CONCLUSIONS: Analysis results indicated that bone was negligibly affected by changing endocrowns and cementing materials. Both tested endocrown materials can be used safely. Zirconia endocrowns may have a much longer lifetime than E-max.
Inhibition of human mitochondrial peptide deformylase (HsPDF) plays a major role in reducing growth, proliferation, and cellular cancer survival. In this work, a series of 32 actinonin derivatives for HsPDF (PDB: 3G5K) inhibitor's anticancer activity was computationally analyzed for the first time, using an in silico study considering 2D-QSAR modeling, and molecular docking studies, and validated by molecular dynamics and ADMET properties. The results of multilinear regression (MLR) and artificial neural networks (ANN) statistical analysis reveal a good correlation between pIC50 activity and the seven (7) descriptors. The developed models were highly significant with cross-validation, the Y-randomization test and their applicability range. In addition, all considered data sets show that the AC30 compound, exhibits the best binding affinity (docking score = -212.074 kcal/mol and H-bonding energy = -15.879 kcal/mol). Furthermore, molecular dynamics simulations were performed at 500 ns, confirming the stability of the studied complexes under physiological conditions and validating the molecular docking results. Five selected actinonin derivatives (AC1, AC8, AC15, AC18 and AC30), exhibiting best docking score, were rationalized as potential leads for HsPDF inhibition, in well agreement with experimental outcomes. Furthermore, based on the in silico study, new six molecules (AC32, AC33, AC34, AC35, AC36 and AC37) were suggested as HsPDF inhibition candidates, which would be combined with in-vitro and in-vivo studies to perspective validation of their anticancer activity. Indeed, the ADMET predictions indicate that these six new ligands have demonstrated a fairly good drug-likeness profile.
Molecular Dynamics Simulation , Neoplasms , Humans , Molecular Docking Simulation , Quantitative Structure-Activity Relationship
Fulvic acid (FA) and humic acid (HA) are common polyacids in nature. However, the evolutionary process of their basic and advanced structures is still unclear. FA and HA were separated into five molecular weight components to investigate the process of evolution from small to large molecules. The primary structure analysis showed that FA were rich in CN, COOH and OH content, while HA were rich in (CH2)n, NH2 and CC. Moreover, with the molecular weight increasing, the structures could complement each other to maintain the hydrophilic or hydrophobic balance. The 2D-COS spectroscopy demonstrated that during the growth of FA, COOH, NH2 and OH firstly respond. On the other hand, during the growth of HA, NH2 and (CH2)n firstly respond. In addition, advanced structure of FA was affected by intramolecular hydrogen bonds and π - π interaction. HA was affected by hydrophobic interactions due to the abundance of hydrophobic groups, primarily (CH2)n and benzene rings. 3D conformational fitting and particle size characterization confirmed that the interaction forces determine that FA and HA become tightly and loosely molecules respectively. This study is to further explore the geochemical formation and evolution process of FA and HA molecules.
Humic Substances , Refuse Disposal , Humic Substances/analysis , Food Loss and Waste , Food , Benzopyrans/chemistry
Exploring alternatives to antibiotics is imperative in reducing antibiotic resistance and antibiotic residues in poultry products. The beneficial effects of antibiotic products derived from natural sources in comparison with the synthetic ones has been reported. Pediococcus pentosaceus has been applied as an animal growth bio-promoter and probiotic. To elucidate the protective mechanisms of P. pentosaceus, this study investigated the effects of different doses of P. pentosaceus supplementation on broiler growth performance, immune function, intestinal development and histomorphology. Five hundred (500) one-day-old Ross 708 broiler chicks were randomly enrolled into five experimental groups with 20 chicks per replicate. The treatments were imposed as follows: (T1) basal diet (control); (T2) basal diet with 1 g/kg antibact 3X; (T3) basal diet with P. pentosaceus GT001 at 4.0 × 108 cfu/g; (T4) basal diet with P. pentosaceus GT001 at 8.0 × 108 cfu/g; and (T5) basal diet with P. pentosaceus GT001 at 1.2 × 109 cfu/g. Dietary inclusion of P. pentosaceus GT001 at 4.0 × 108 cfu/g significantly improved body weight gain, feed intake and lipid profile of the broilers compared to the control group (p < 0.05). The addition of P. pentosaceus GT001 significantly improved the intestinal pH of the broilers. The digestive enzymes of the broilers were impacted with the supplementation of P. pentosaceus GT001 at 4.0 × 108 cfu/g. The highest serum antioxidant production was observed in the P. pentosaceus-treated group compared to the control. P. pentosaceus GT001 at 4.0 × 108 cfu/g increased the levels of serum cytokines and immunoglobin and improved the small intestinal morphology of the broilers in comparison with the control. The load of Pedococcus spp was similar among T3, T4 and T5 but significantly higher than that of the control (T1) and the antibiotics (T2)-fed birds. The load of E. coli in the gut was significantly reduced in T3, T4 and T5 compared to T1 and T2. There was no Salmonella growth among the treatments. This study highlights the importance of probiotics in broiler diets and suggests that Pediococcus pentosaceus GT001 could be used as a feasible substitute to antimicrobials in broiler production.
Human mitochondrial (mt) protein assemblies are vital for neuronal and brain function, and their alteration contributes to many human disorders, e.g., neurodegenerative diseases resulting from abnormal protein-protein interactions (PPIs). Knowledge of the composition of mt protein complexes is, however, still limited. Affinity purification mass spectrometry (MS) and proximity-dependent biotinylation MS have defined protein partners of some mt proteins, but are too technically challenging and laborious to be practical for analyzing large numbers of samples at the proteome level, e.g., for the study of neuronal or brain-specific mt assemblies, as well as altered mtPPIs on a proteome-wide scale for a disease of interest in brain regions, disease tissues or neurons derived from patients. To address this challenge, we adapted a co-fractionation-MS platform to survey native mt assemblies in adult mouse brain and in human NTERA-2 embryonal carcinoma stem cells or differentiated neuronal-like cells. The workflow consists of orthogonal separations of mt extracts isolated from chemically cross-linked samples to stabilize PPIs, data-dependent acquisition MS to identify co-eluted mt protein profiles from collected fractions and a computational scoring pipeline to predict mtPPIs, followed by network partitioning to define complexes linked to mt functions as well as those essential for neuronal and brain physiological homeostasis. We developed an R/CRAN software package, Macromolecular Assemblies from Co-elution Profiles for automated scoring of co-fractionation-MS data to define complexes from mtPPI networks. Presently, the co-fractionation-MS procedure takes 1.5-3.5 d of proteomic sample preparation, 31 d of MS data acquisition and 8.5 d of data analyses to produce meaningful biological insights.
Mitochondrial Proteins , Proteome , Animals , Mice , Humans , Proteome/analysis , Proteomics/methods , Mass Spectrometry/methods , Brain , Neurons , Mammals
The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.
BACKGROUND: Melatonin might be beneficial to coronavirus disease 2019 (COVID-19) patients in terms of both prevention and treatment. We investigated how melatonin affected various clinical and laboratory results in COVID-19 patients. METHODS: PubMed, Scopus, Cochrane Library and Web of Science databases were utilized for searching eligible articles fulfilling our inclusion criteria up to December 2022. We used random effect model in case of significant heterogeneity; in other cases, a fixed model was applied. RevMan was used for meta-analysis. RESULTS: We included 11 studies in our review. Clinical improvement rate was found to be statistically significantly higher in patients taking melatonin than in the control group (OR: 5.09; 95% CI: 2.60-9.96, p â< â0.001). Patients receiving melatonin showed a non-significant difference in mortality rate compared to the control group (OR: 0.37; 95% CI: 0.07-1.81, p â= â0.22). However, in the randomized controlled trials subgroup, melatonin-treated patients showed significantly lower mortality than did the controls (OR: 0.17; 95% CI: 0.08-0.38, p â< â0.001). CRP level was statistically significantly lower due to melatonin treatment (weighted mean difference [WMD] â= â-9.85; 95% CI: -18.54 to -1.16, p â= â0.03). Length of hospital stay was statistically significantly shorter in patients taking melatonin compared to controls (WMD â= â-4.05; 95% CI: -5.39 to -2.7, p â< â0.001). CONCLUSION: Melatonin was found to have substantial effects on COVID-19 patients when used as adjuvant therapy, enhancing clinical improvement and decreasing time to recovery with a shorter length of hospital stay and a shorter duration of mechanical ventilation.
COVID-19 , Melatonin , Humans , Melatonin/therapeutic use , Length of Stay
BACKGROUND: Taxane-induced peripheral neuropathy (TIPN) among breast cancer patients is considered one of the most devastating side effects affecting compliance to chemotherapy protocol and patients' quality of life (QOL). OBJECTIVES: This trial aimed to evaluate the effect of lidocaine infusion vs oral duloxetine on the incidence and severity of TIPN and QOL in patients with breast cancer scheduled for neoadjuvant taxane therapy (TT). STUDY DESIGN: Prospective, randomized, single-blinded, controlled trial. SETTING: This study was carried out on 60 patients with breast cancer scheduled for 12 weeks of TT at the Medical Research Institute Hospital, Alexandria University after obtaining local Ethics Committee approval (IORG008812) and getting a written informed consent from each patient. It was registered in the "clinical trials library for protocol registration and results system" with the number NCT04732455. METHODS: Sixty women scheduled for TT weekly for 12 weeks, were randomly allocated to receive intravenous saline infusion in the control group (GC), or lidocaine 2mg/kg with saline infusion in the lidocaine group (GL), or saline infusion and 30 mg duloxetine in the duloxetine group (GD). All infusions were administered over 40 minutes before each TT. Oral duloxetine was prescribed once daily starting from the night before commencing TT and continued for 12 weeks. Douleur Neuropathique en 4 Questions (DN4) questionnaire was filled weekly to detect the incidence of neuropathic pain (NP). The nerve conduction study (NCS) aimed to detect and measure the degree of neuropathy before starting the chemotherapy protocol and post-12 weeks of Taxol Therapy. NP Scale was measured weekly to assess the severity of NP symptoms. Patients' QOL was evaluated by the European Organization for Research and Treatment of Cancer QOL Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale. RESULTS: Thirty-five percent of patients reported DN4 > 4 points in GC after 6 weeks of TT in comparison to 5% in GL and 0% in GD (P = .005). Moreover, the incidence rose to 75% in GC compared to 20% in GL and 25% GD at the end of TT (P < 0.001). The severity of symptoms, global pain intensity, and patients' unpleasantness were significantly more in GC than GL and GD in the last 4 weeks of TT (P < 0.05). NCS showed that 55% and 25% of patients developed mild and moderate axonal neuropathy, respectively, in GC. In contrast, mild neuropathy was developed in 20% and 25% of patients in GL and GD, respectively, and moderate neuropathy in 5% in both groups. The negative impact of TT on QOL was more significant in GC than GL and GD at weeks 8 and 12 of TT (P < 0.001). LIMITATIONS: Limited reference data for all treatment regimens to include in the Discussion section. CONCLUSIONS: Lidocaine and duloxetine have a comparable effect to decrease the incidence and severity of TIPN. Moreover, patients' QOL was significantly better in both groups. KEY WORDS: Lidocaine infusion, duloxetine, taxane-induced peripheral neuropathy, breast cancer, DN4.
Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.
The high prevalence of fungal resistance to antifungal drugs necessitates finding new antifungal combinations to boost the antifungal bioactivity of these agents. Hence, the aim of the present investigation was to greenly synthesize zinc oxide nanoparticles (ZnO-NPs) using an aqueous leaf extract of Salvia officinalis and investigate their antifungal activity and synergistic efficiency with common antifungal agents. The biofabricated ZnO-NPs were characterized to detect their physicochemical properties. A disk diffusion assay was employed to investigate the antifungal effectiveness of the greenly synthesized ZnO-NPs and evaluate their synergistic patterns with common antifungal agents. The Candida tropicalis strain was detected to be the most susceptible strain to ZnO-NPs at both tested concentrations of 50 and 100 µg/disk, demonstrating relative suppressive zones of 19.68 ± 0.32 and 23.17 ± 0.45 mm, respectively. The minimum inhibitory concentration (MIC) of ZnO-NPs against the C. tropicalis strain was 40 µg/mL, whereas the minimum fungicidal concentration (MFC) was found to be 80 µg/mL. The highest synergistic efficiency of the biogenic ZnO-NPs with terbinafine antifungal agent was detected against the C. glabrata strain, whereas the highest synergistic efficiency was detected with fluconazole against the C. albicans strain, demonstrating relative increases in fold of inhibition area (IFA) values of 6.82 and 1.63, respectively. Moreover, potential synergistic efficiency was detected with the nystatin antifungal agent against the C. tropicalis strain with a relative IFA value of 1.06. The scanning electron microscopy (SEM) analysis affirmed the morphological deformations of candidal cells treated with the biosynthesized ZnO-NPs as the formation of abnormal infoldings of the cell wall and membranes and also the formation of pores in the cell wall and membranes, which might lead to the leakage of intracellular constituents. In conclusion, the potential synergistic efficiency of the biogenic ZnO-NPs with terbinafine, nystatin, and fluconazole against the tested candidal strains highlights the potential application of these combinations in formulating novel antifungal agents of high antimicrobial efficiency. The biogenic ZnO nanoparticles and antifungal drugs exhibit powerful synergistic efficiency, which highlights their prospective use in the formulation of efficient antimicrobial medications, including mouthwash, ointments, lotions, and creams for effective candidiasis treatment.
Reactive oxygen species (ROS) are common products of normal cellular metabolism, but their elevated levels can result in nucleotide modifications. These modified or noncanonical nucleotides often integrate into nascent DNA during replication, causing lesions that trigger DNA repair mechanisms such as the mismatch repair machinery and base excision repair. Four superfamilies of sanitization enzymes can effectively hydrolyze noncanonical nucleotides from the precursor pool and eliminate their unintended incorporation into DNA. Notably, we focus on the representative MTH1 NUDIX hydrolase, whose enzymatic activity is ostensibly nonessential under normal physiological conditions. Yet, the sanitization attributes of MTH1 are more prevalent when ROS levels are abnormally high in cancer cells, rendering MTH1 an interesting target for developing anticancer treatments. We discuss multiple MTH1 inhibitory strategies that have emerged in recent years, and the potential of NUDIX hydrolases as plausible targets for the development of anticancer therapeutics.
Nucleotides , Nudix Hydrolases , Phosphoric Monoester Hydrolases , Reactive Oxygen Species , Antineoplastic Agents , Humans , Reactive Oxygen Species/metabolism , DNA Repair Enzymes , Nucleotides/genetics , Nucleotides/metabolism
It was assumed that dietary inclusion of Lactobacillus reuteri SL001 isolated from the gastric contents of rabbits could act as an alternative to feed antibiotics to improve the growth performance of broiler chickens. We randomly assigned 360 one-day-old AA white-feathered chicks in three treatments: basal diet (control), basal diet plus zinc bacitracin (antibiotic), and basal diet plus L. reuteri SL001 (SL001) treatment. The results showed the total BW gain and average daily gain (ADG) of broilers in SL001 treatment increased significantly (p < 0.05, respectively) compared with the control group from day 0 to 42. Moreover, we observed higher levels of immune globulins in both the SL001 group and the antibiotic group. Total antioxidant capacity and levels of antioxidant factors were also significantly increased (p ≤ 0.05, respectively) in the SL001 treatment group, while the interleukin 6, interleukin 4, creatinine, uric acid, total cholesterol, triglyceride, VLDL, LDL and malondialdehyde were remarkably decreased (p < 0.05, respectively). In the ileum of SL001 treatment broilers, the height of villi and the ratio of villi height to crypt depth were significantly increased (p < 0.05). Meanwhile, the crypt depth reduced (p < 0.01) and the ratio of villi height to crypt depth increased (p < 0.05) in the jejunum compared to the control. The abundance of microbiota increased in the gut of broilers supplemented with SL001. Dietary SL001 significantly increased the relative abundance of Actinobacteria in the cecal contents of broilers (p < 0.01) at the phylum level. In conclusion, L. reuteri SL001 supplementation promotes the growth performance of broiler chickens and exhibits the potential application value in the industry of broiler feeding.
Mitochondria possess their own DNA (mtDNA) and are capable of carrying out their transcription and translation. Although protein synthesis can take place in mitochondria, the majority of the proteins in mitochondria have nuclear origin. 3' and 5' untranslated regions of mRNAs (3'-UTR and 5'-UTR, respectively) are thought to play key roles in directing and regulating the activity of mitochondria mRNAs. Here we investigate the association between the presence of 3'-UTR from OXA1 gene on a prokaryotic reporter mRNA and mitochondrial translation in yeast. OXA1 is a nuclear gene that codes for mitochondrial inner membrane insertion protein and its 3'-UTR is shown to direct its mRNA toward mitochondria. It is not clear, however, if this mRNA may also be translated by mitochondria. In the current study, using a ß-galactosidase reporter gene, we provide genetic evidence for a correlation between the presence of 3'-UTR of OXA1 on an mRNA and mitochondrial translation in yeast.
Nosocomial bacterial and fungal infections are one of the main causes of high morbidity and mortality worldwide, owing to the high prevalence of multidrug-resistant microbial strains. Hence, the study aims to synthesize, characterize, and investigate the antifungal and antibacterial activity of silver nanoparticles (AgNPs) fabricated using Camellia sinensis leaves against nosocomial pathogens. The biogenic AgNPs revealed a small particle diameter of 35.761 ± 3.18 nm based on transmission electron microscope (TEM) graphs and a negative surface charge of -14.1 mV, revealing the repulsive forces between nanoparticles, which in turn indicated their colloidal stability. The disk diffusion assay confirmed that Escherichia coli was the most susceptible bacterial strain to the biogenic AgNPs (200 g/disk), while the lowest sensitive strain was found to be the Acinetobacter baumannii strain with relative inhibition zones of 36.14 ± 0.67 and 21.04 ± 0.19 mm, respectively. On the other hand, the biogenic AgNPs (200 µg/disk) exposed antifungal efficacy against Candida albicans strain with a relative inhibition zone of 18.16 ± 0.14 mm in diameter. The biogenic AgNPs exposed synergistic activity with both tigecycline and clotrimazole against A. baumannii and C. albicans, respectively. In conclusion, the biogenic AgNPs demonstrated distinct physicochemical properties and potential synergistic bioactivity with tigecycline, linezolid, and clotrimazole against gram-negative, gram-positive, and fungal strains, respectively. This is paving the way for the development of effective antimicrobial combinations for the effective management of nosocomial pathogens in intensive care units (ICUs) and health care settings.
Several indicators of fecal pollution in water resources are continuously monitored for their reliability and, of particular interest, their correlation to human enteric viruses-not justified by traditional bacterial indicators. Pepper mild mottle virus (PMMoV) has recently been proposed as a successful viral surrogate of human waterborne viruses; however, in Saudi Arabia there are no available data in terms of its prevalence and concentration in water bodies. The concentration of PMMoV in three different wastewater treatment plants (King Saud University (KSU), Manfoha (MN), and Embassy (EMB) wastewater treatment plants (WWTP)) was measured using qRT-PCR during a one-year period and compared to the human adenovirus (HAdV), which is highly persistent and considered an indicator for viral-mediated fecal contamination. PMMoV was found in ~94% of the entire wastewater samples (91.6-100%), with concentrations ranging from 62 to 3.5 × 107 genome copies/l (GC/l). However, HAdV was detected in 75% of raw water samples (~67-83%). The HAdV concentration ranged between 1.29 × 103 GC/L and 1.26 × 107 GC/L. Higher positive correlation between PMMoV and HAdV concentrations was detected at MN-WWTP (r = 0.6148) than at EMB-WWTP (r = 0.207). Despite the lack of PMMoV and HAdV seasonality, a higher positive correlation (r = 0.918) of PMMoV to HAdV was recorded at KSU-WWTP in comparison to EMB-WWTP (r = 0.6401) around the different seasons. Furthermore, meteorological factors showed no significant influence on PMMoV concentrations (p > 0.05), thus supporting the use of PMMoV as a possible fecal indicator of wastewater contamination and associated public health issues, particularly at MN-WWTP. However, a continuous monitoring of the PMMoV distribution pattern and concentration in other aquatic environments, as well as its correlation to other significant human enteric viruses, is essential for ensuring its reliability and reproducibility as a fecal pollution indicator.
