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1.
Chem Rev ; 123(8): 4443-4509, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37067292

ABSTRACT

Energy from renewable resources is central to environmental sustainability. Among the renewables, sunlight-driven fuel synthesis is a sustainable and economical approach to produce vectors such as hydrogen through water splitting. The photocatalytic water splitting is limited by the water oxidation half-reaction, which is kinetically and energetically demanding and entails designer photocatalysts. Such challenges can be addressed by employing alternative oxidation half-reactions. Photoreforming can drive the breakdown of waste plastics and biomass into valuable organic products for the production of H2. We provide an overview of photoreforming and its underlying mechanisms that convert waste polymers into H2 fuels and fine chemicals. This is of paramount importance from two complementary perspectives: (i) green energy harvesting and (ii) environmental sustainability by decomposing waste polymers into valuables. Competitive results for the generation of H2 fuel without environmental hazards through photoreforming are being generated. The photoreforming process, mechanisms, and critical assessment of the field are scarce. We address such points by focusing on (i) the concept of photoreforming and up-to-date knowledge with key milestones achieved, (ii) uncovering the concepts and challenges in photoreforming, and (iii) the design of photocatalysts with underlying mechanisms and pathways through the use of different polymer wastes as substrates.

2.
Arterioscler Thromb Vasc Biol ; 43(8): 1429-1440, 2023 08.
Article in English | MEDLINE | ID: mdl-37381986

ABSTRACT

BACKGROUND: Increasing evidence suggests that superoxide ions produced by NOX (nicotinamide adenine dinucleotide phosphate oxidases) mediate vascular effects of Ang II (angiotensin II) evoked by atherogenic diets. Here, we analyzed the mechanism by which NOX2 contributes to Ang II-induced ET-1 (endothelin 1) production in human microvascular endothelial cells. METHODS: The effects of high-fat diet were compared between WT (wild type) and Nox2 (mouse NOX2 gene)-deficient mice. ET-1 production and NOX2 expression by human microvascular endothelial cells in vitro were analyzed by ELISA, reverse transcription quantitative polymerase chain reaction, electrophoretic mobility shift assay, promoter deletions, RNA interference, and pharmacological inhibition. Production of superoxide anions was visualized by fluorescent cell labeling. RESULTS: Feeding mice high-fat diet for 10 weeks increased cardiac expression and plasma levels of Ang II and ET-1 in WT but not in Nox2-deficient animals. Exposure of human microvascular endothelial cells to Ang II resulted in increased ET-1 production, which could be blocked by silencing NOX2 (human NOX2 gene). Ang II promoted NOX2 expression through induction of the Oct-1 (human/mouse octamer binding transcription factor 1 protein) and activation of the NOX2 promoter region containing Oct-1-binding sites. Stimulation of NOX2 expression by Ang II was associated with increased production of superoxide anions. Inhibition of Oct-1 by small interfering RNA reduced Ang II-induced NOX2 expression and superoxide anion production, and neutralization of superoxide by SOD (superoxide dismutase) abolished Ang II-stimulated ET1 (human ET-1 gene) promoter activity, ET1 mRNA expression, and ET-1 release. CONCLUSIONS: Ang II may promote ET-1 production in the endothelium in response to atherogenic diets through a mechanism that involves the transcription factor Oct-1 and the increased formation of superoxide anions by NOX2.


Subject(s)
Endothelial Cells , Superoxides , Mice , Animals , Humans , Superoxides/metabolism , Endothelial Cells/metabolism , Octamer Transcription Factor-1 , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , Angiotensin II/pharmacology , Angiotensin II/metabolism , Reactive Oxygen Species/metabolism
3.
Pacing Clin Electrophysiol ; 47(1): 156-166, 2024 01.
Article in English | MEDLINE | ID: mdl-38071452

ABSTRACT

BACKGROUND: This meta-analysis compares His-Purkinje system pacing (HPSP), a novel cardiac resynchronization therapy (CRT) technique that targets the intrinsic conduction system of the heart, with conventional biventricular pacing (BiVP) in heart failure (HF) patients with left ventricular (LV) dysfunction and dyssynchrony. METHODS: We searched multiple databases up to May 2023 and identified 18 studies (five randomized controlled trials and 13 observational studies) involving 1291 patients. The outcome measures were QRS duration, left ventricular ejection fraction (LVEF) improvement, left ventricular end-diastolic diameter (LVEDD) change, HF hospitalization, and New York Heart Association (NYHA) functional class improvement. We used a random-effects model to calculate odds ratios (OR), and mean differences (MD) with 95% confidence intervals (CI). We also assessed the methodological quality of the studies. RESULTS: The mean LVEF was 30.7% and the mean follow-up duration was 8.1 months. Among LBBP, HBP, and BiVP, HBP provided the shortest QRS duration [MD: -18.84 ms, 95% CI: -28.74 to -8.94; p = 0.0002], while LBBP showed the greatest improvement in LVEF [MD: 5.74, 95% CI: 2.74 to 7.46; p < 0.0001], LVEDD [MD: -5.55 mm, 95% CI: -7.51 to -3.59; p < 0.00001], and NYHA functional class [MD: -0.58, 95% CI: -0.80 to --0.35; p < 0.00001]. However, there was no significant difference in HF hospitalization between HPSP and BiVP. CONCLUSION: LBBP as modality of HPSP demonstrated superior outcomes in achieving electrical ventricular synchrony and systolic function, as well as alleviating HF symptoms, compared to other pacing techniques.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Humans , Cardiac Resynchronization Therapy/methods , Stroke Volume , Ventricular Function, Left , Treatment Outcome , Bundle of His , Electrocardiography/methods , Cardiac Pacing, Artificial/methods
4.
Bioorg Chem ; 143: 106984, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38056389

ABSTRACT

Inflammation is a multifaceted phenomenon triggered by potentially active mediators acutely released arachidonic acid metabolites partially in lipoxygenase (LOX) pathway which are primarily accountable for causing several diseases in humans. It is widely believed that an inhibitor of the LOX pathway represents a rational approach for designing more potent antiinflammatory leads with druggable super safety profiles. In our continual efforts in search for anti-LOX molecules, the present work was to design a new series of N-alkyl/aralkyl/aryl derivatives (7a-o) of 4-phenyl-5-(1-phenylcarbamoylpiperidine)-4H-1,2,4-triazole-3-thiol which was commenced in seriate formation of phenylcarbamoyl derivative (1), hydrazide (2), semicarbazide (3) and 4-phenyl-5-(1-phenylcarbamoylpiperidine)-4H-1,2,4-triazole-3-thiol (4). The aimed compounds were obtained by reacting 4-phenyl-5-(1-phenylcarbamoylpiperidine)-4H-1,2,4-triazole-3-thiol with assorted N-alkyl/aralkyl/aryl electrophiles. All compounds were characterized by FTIR, 1H-, 13C-NMR spectroscopy, EI-MS and HR-EI-MS spectrometry and screened against soybean 15-LOX for their inhibitory potential using chemiluminescence method. All the compounds except 7m and 7h inhibited the said enzyme remarkably. Compounds 7c,7l, 7j and 7a displayed potent inhibitions ranging from IC50 1.92 ± 0.13 µM to 7.65 ± 0.12 µM. Other analogues 7g, 7o, 7e, 7b, 7d, 7k and 7n revealed excellent inhibitory values ranging from IC50 12.45 ± 0.38 µM to 24.81 ± 0.47 µM. All these compounds did not reveal DPPH radical scavenging activity. Compounds 7i-o maintained > 90 % human blood mononuclear cells (MNCs) viability at 0.125 mM as assayed by MTT whilst others were found toxic. Pharmacokinetic profiles predicted good oral bioavailability and drug-likeness properties of the active scaffolds. SAR investigations showed that phenyl substituted analogue on amide side decreased inhibitory activity due to inductive and mesomeric effects while the mono-alkyl substituted analogues were more active than disubstituted ones and ortho substituted analogues were more potent than meta substituted ones. MD simulation predicted the stability of the 7c ligand and receptor complex as shown by their relative RMSD (root mean square deviation) values. Molecular docking studies displayed hydrogen bonding between the compounds and the enzyme with Arg378 which was common in 7n, 7g, 7h and baicalein. In 7a and quercetin, hydrogen bonding was established through Asn375. RMSD values exhibited good inhibitory profiles in the order quercetin (0.73 Å) < 7 g < baicalein < 7a < 7n < 7 h (1.81 Å) and the binding free energies followed similar pattern. Density functional theory (DFT) data established good correlation between the active compounds and significant activity was associated with more stabilized LUMO (lowest unoccupied molecular orbitals) orbitals. Nevertheless, the present studies declare active analogues like 7c, 7 l, 7a, 7j as leads. Work is ongoing in derivatizing active molecules to explore more effective leads as 15-LOX inhibitors as antiinflammatory agents.


Subject(s)
Lipoxygenase Inhibitors , Quercetin , Triazoles , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Density Functional Theory , Lipoxygenase Inhibitors/pharmacology , Lipoxygenase Inhibitors/chemistry , Sulfhydryl Compounds , Molecular Structure
5.
Appl Microbiol Biotechnol ; 108(1): 274, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530495

ABSTRACT

The pharmaceutical industry employs various strategies to improve cell productivity. These strategies include process intensification, culture media improvement, clonal selection, media supplementation and genetic engineering of cells. However, improved cell productivity has inherent risk of impacting product quality attributes (PQA). PQAs may affect the products' efficacy via stability, bioavailability, or in vivo bioactivity. Variations in manufacturing process may introduce heterogeneity in the products by altering the type and extent of N-glycosylation, which is a PQA of therapeutic proteins. We investigated the effect of different cell densities representing increasing process intensification in a perfusion cell culture on the production of an IgG1-κ monoclonal antibody from a CHO-K1 cell line. This antibody is glycosylated both on light chain and heavy chain. Our results showed that the contents of glycosylation of IgG1-κ mAb increased in G0F and fucosylated type glycans as a group, whereas sialylated type glycans decreased, for the mAb whole protein. Overall, significant differences were observed in amounts of G0F, G1F, G0, G2FS1, and G2FS2 type glycans across all process intensification levels. G2FS2 and G2 type N-glycans were predominantly quantifiable from light chain rather than heavy chain. It may be concluded that there is a potential impact to product quality attributes of therapeutic proteins during process intensification via perfusion cell culture that needs to be assessed. Since during perfusion cell culture the product is collected throughout the duration of the process, lot allocation needs careful attention to process parameters, as PQAs are affected by the critical process parameters (CPPs). KEY POINTS: • Molecular integrity may suffer with increasing process intensity. • Galactosylated and sialylated N-glycans may decrease. • Perfusion culture appears to maintain protein charge structure.


Subject(s)
Antibodies, Monoclonal , Immunoglobulin G , Cricetinae , Animals , CHO Cells , Cricetulus , Perfusion , Polysaccharides/chemistry
6.
Article in English | MEDLINE | ID: mdl-38693698

ABSTRACT

INTRODUCTION: Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child. MATERIAL AND METHODS: We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term. RESULTS: Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study. CONCLUSIONS: Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

7.
Curr Microbiol ; 81(8): 260, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980435

ABSTRACT

Viral diseases are a serious threat to humans while the most antiviral drugs have low efficiency and side effects on human health. Therefore, using microbial biopolymers as the drugs alternate to treat viral infections seems cost-effective and human friendly option. In the present study, thirty-four exopolysaccharides (EPSs) producing bacteria were isolated, and EPSs production capacity of five salt-tolerant isolates was determined under 0, 100 and 150 mM NaCl. Among these, two isolates exhibiting high anti-coliphage activity were identified through 16S rRNA gene analysis. Moreover, the EPSs were characterized by Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, and their composition was determined. Five salt-tolerant bacteria (MK1, MK2, MK10, MK22 and MK29) exhibited higher production of EPSs at 100 mM NaCl compared to that under non-saline control. At 100 mM NaCl, the yield of EPSs ranged between 105 and 330 mg 100 mL-1 broth. The EPSs produced by the isolates MK1 and MK2 exhibited higher anti-coliphage activity (plaque forming unit decreased from 43 × 106 mL-1 to 3 × 106 and 4 × 106 mL-1, respectively), and were comprised of glucose, fructose, galactose, sucrose, lactose and xylose sugars. FTIR spectroscopy depicted that EPSs are mainly composed of hydroxyl, aliphatic, carboxyl, sulfate and phosphate functional groups, which could have bound coliphage and thus conferred higher anti-coliphage activities to the EPSs. Phylogenetic analysis revealed that MK1 and MK2 isolates formed clades within genus Priestia and Bacillus sequences, respectively. High EPSs production capacity of bacterial isolates under saline condition and high anti-coliphage activity of the EPSs implies that bacterial biopolymers could be useful in antiviral drugs therapy.


Subject(s)
Antiviral Agents , Bacillus , Polysaccharides, Bacterial , RNA, Ribosomal, 16S , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , RNA, Ribosomal, 16S/genetics , Bacillus/genetics , Bacillus/metabolism , Bacillus/chemistry , Bacillus/classification , Phylogeny , Spectroscopy, Fourier Transform Infrared , Sodium Chloride/pharmacology , Sodium Chloride/metabolism
8.
Ecotoxicol Environ Saf ; 269: 115791, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38070417

ABSTRACT

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.


Subject(s)
Alkaloids , Aluminum , Aluminum/toxicity , Aluminum/metabolism , Malates/metabolism , Plant Breeding , Plants/metabolism , Alkaloids/pharmacology , Organic Chemicals/metabolism , Soil/chemistry , Plant Roots/metabolism , Gene Expression Regulation, Plant
9.
Int J Neurosci ; : 1-2, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38758121

ABSTRACT

Autism Spectrum disorder is a significant neurodevelopmental behavioral disorder. Children with Autism display a wide array of ambiguous symptoms resulting making the diagnosis quite challenging thus resulting in delayed management. Traditionally, its diagnosis and management require the collaboration of services from the three P's namely the pediatrician, psychiatrist, and child psychologist. The management requires an intensive multi-disciplinary approach which would help minimize the disease symptoms and facilitate development and learning during childhood.Recently, with the advent of widespread testing and usage of various artificial intelligence tools across various domains, AI tools such as Chatbots are being incorporated into medical treatments, especially in behavioral therapy. Considering the increasing use of AI, we believe that the natural language processing techniques employed by ChatGPT algorithms have the potential to identify speech and linguistic patterns in children with ASD. Therefore, through this letter, we have tried to explore the scope of Artificial intelligence (ChatGPT) for behavioral therapy in children affected with autism spectrum disorder.

10.
Int J Phytoremediation ; 26(6): 913-927, 2024.
Article in English | MEDLINE | ID: mdl-37985450

ABSTRACT

Salt excretory halophytes are the major sources of phytoremediation of salt-affected soils. Cressa cretica is a widely distributed halophyte in hypersaline lands in the Cholistan Desert. Therefore, identification of key physio-anatomical traits related to phytoremediation in differently adapted C. cretica populations was focused on. Four naturally adapted ecotypes of non-succulent halophyte Cressa cretica L. form hyper-arid and saline desert Cholistan. The selected ecotypes were: Derawar Fort (DWF, ECe 20.8 dS m-1) from least saline site, Traway Wala Toba (TWT, ECe 33.2 dS m-1) and Bailah Wala Dahar (BWD, ECe 45.4 dS m-1) ecotypes were from moderately saline sites, and Pati Sir (PAS, ECe 52.4 dS m-1) was collected from the highly saline site. The natural population of this species was collected and carefully brought to the laboratory for different structural and functional traits. As a result of high salinity, Na+, Cl-, K+, and Ca2+ content significantly increased at root and shoot level. At root level, some distinctive modifications such as increased sclerification in vascular bundles, enlarged vascular bundles, metaxylem vessels, phloem region, and storage parenchyma (cortex) are pivotal for water storage under extreme arid and osmotic condition. At the stem level, enhanced sclerification in outer cortex and vascular bundles, stem cellular area, cortical proportion, metaxylem and phloem area, and at the leaf level, very prominent structural adaptations were thicker and smaller leaves with increased density of salt glands and trichomes at surface, few and large stomata, reduced cortical and mesophyll parenchyma, and narrow xylem vessels and phloem area represent their non-succulent nature. The ecotype collected from hypersaline environments was better adapted regarding growth traits, ion uptake and excretion, succulence, and phytoremediation traits. More importantly, structural and functional traits such as root length and biomass, accumulation of toxic ions along with K+ in root and shoot, accumulation of Ca2+ in shoot and Mg2+ in root, excretion of toxic ions were the highest in this ecotype. In conclusion, all these alterations strongly favor water conservation, which certainly contributes to ecotypes survival under salt-induced physiological drought.


Naturally adapted salt tolerant plants provide exceptional material for exploring adaptive mechanisms they use to confront high salt concentrations. Cressa cretica is a hypersaline hyperarid desert colonizer, which was previously underexplored. In the present study, we focused on the new insight on relationship among anatomical modifications, salt accumulation and excretion and phytoremediation potential of this rare species.


Subject(s)
Alkalies , Soil , Biodegradation, Environmental , Soil/chemistry , Saline Solution , Sodium Chloride , Ions , Salt-Tolerant Plants/chemistry , Salt-Tolerant Plants/physiology , Salinity
11.
J Environ Manage ; 351: 119759, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38091729

ABSTRACT

While it is widely recognized that hydrogen sulfide (H2S) promotes plant stress tolerance, the precise processes through which H2S modulates this process remains unclear. The processes by which H2S promotes phosphorus deficiency (PD) and salinity stress (SS) tolerance, simulated individually or together, were examined in this study. The adverse impacts on plant biomass, total chlorophyll and chlorophyll fluorescence were more pronounced with joint occurrence of PD and SS than with individual application. Malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL) levels in plant leaves were higher in plants exposed to joint stresses than in plants grown under an individual stress. When plants were exposed to a single stress as opposed to both stressors, sodium hydrosulfide (NaHS) treatment more efficiently decreased EL, MDA, and H2O2 concentrations. Superoxide dismutase, peroxidase, glutathione reductase and ascorbate peroxidase activities were increased by SS alone or in conjunction with PD, whereas catalase activity decreased significantly. The favorable impact of NaHS on all the evaluated attributes was reversed by supplementation with 0.2 mM hypotaurine (HT), a H2S scavenger. Overall, the unfavorable effects caused to NaHS-supplied plants by a single stress were less severe compared with those caused by the combined administration of both stressors.


Subject(s)
Capsicum , Hydrogen Sulfide , Sulfides , Hydrogen Sulfide/pharmacology , Hydrogen Peroxide , Antioxidants , Chlorophyll , Dietary Supplements , Phosphates , Seedlings
12.
J Cell Biochem ; 124(8): 1082-1104, 2023 08.
Article in English | MEDLINE | ID: mdl-37566723

ABSTRACT

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.


Subject(s)
Neoplasms , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/genetics , Killer Cells, Natural , Neoplasms/pathology , Immunotherapy, Adoptive , Immunotherapy
13.
Kidney Int ; 104(1): 90-107, 2023 07.
Article in English | MEDLINE | ID: mdl-37121432

ABSTRACT

The polyamines spermidine and spermine and their common precursor molecule putrescine are involved in tissue injury and repair. Here, we test the hypothesis that impaired polyamine homeostasis contributes to various kidney pathologies in mice during experimental models of ischemia-reperfusion, transplantation, rhabdomyolysis, cyclosporine treatment, arterial hypertension, diabetes, unilateral ureteral obstruction, high oxalate feeding, and adenine-induced injuries. We found a remarkably similar pattern in most kidney pathologies with reduced expression of enzymes involved in polyamine synthesis together with increased expression of polyamine degrading enzymes. Transcript levels of amine oxidase copper-containing 1 (Aoc1), an enzyme which catalyzes the breakdown of putrescine, were barely detectable by in situ mRNA hybridization in healthy kidneys. Aoc1 was highly expressed upon various experimental kidney injuries resulting in a significant reduction of kidney putrescine content. Kidney levels of spermine were also significantly reduced, whereas spermidine was increased in response to ischemia-reperfusion injury. Increased Aoc1 expression in injured kidneys was mainly accounted for by an Aoc1 isoform that harbors 22 additional amino acids at its N-terminus and shows increased secretion. Mice with germline deletion of Aoc1 and injured kidneys showed no decrease of kidney putrescine content; although they displayed no overt phenotype, they had fewer tubular casts upon ischemia-reperfusion injury. Hyperosmotic stress stimulated AOC1 expression at the transcriptional and post-transcription levels in metanephric explants and kidney cell lines. AOC1 expression was also significantly enhanced after kidney transplantation in humans. These data demonstrate that the kidneys respond to various forms of injury with down-regulation of polyamine synthesis and activation of the polyamine breakdown pathway. Thus, an imbalance in kidney polyamines may contribute to various etiologies of kidney injury.


Subject(s)
Amine Oxidase (Copper-Containing) , Reperfusion Injury , Humans , Mice , Animals , Polyamines/metabolism , Spermidine/metabolism , Putrescine/metabolism , Spermine/metabolism , Spermine/pharmacology , Acetyltransferases/genetics , Acetyltransferases/metabolism , Kidney/pathology , Amine Oxidase (Copper-Containing)/metabolism , Reperfusion Injury/pathology , Gene Expression
14.
Microb Pathog ; 185: 106401, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37858634

ABSTRACT

In this study, we checked the effectiveness of L. fermentum IKP 111 in treating S. enteritidis infection in an in vivo study. Its oral administration to broiler chicks significantly reduced the colonization of S. enteritidis in the gut and there was a lower bacterial count of S. enteritidis in the droppings after infection. The administration of the probiotic L. fermentum IKP 111 also led to increase in weight gain in the broiler chicks as well as their immunomodulation against avian influenza virus (AIV) and Newcastle disease virus (NDV) as compared to the chicks challenged only with S. enteritidis. Our study provides evidence that the probiotic strain L. fermentum IKP 111 could be an alternate for controlling S. enteritidis infection while enhancing the gut health as well as the immune response of broiler chickens against viral infections.


Subject(s)
Limosilactobacillus fermentum , Poultry Diseases , Probiotics , Salmonella Infections, Animal , Animals , Salmonella enteritidis , Chickens/microbiology , Poultry Diseases/microbiology , Salmonella Infections, Animal/microbiology
15.
Diabetes Obes Metab ; 25(11): 3377-3389, 2023 11.
Article in English | MEDLINE | ID: mdl-37580969

ABSTRACT

AIM: Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. METHODS: A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. RESULTS: In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. CONCLUSION: The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.


Subject(s)
Diabetes Mellitus, Type 1 , Humans , Adolescent , Diabetes Mellitus, Type 1/drug therapy , Antibodies, Monoclonal/therapeutic use , Insulin/therapeutic use , Chronic Disease , C-Peptide
16.
Environ Res ; 223: 115448, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36773638

ABSTRACT

Soil salinity and Fe deficiency affect plant growth and survival by changing nutrient availability and disrupting water balance. Natural and human activities, such as evaporation and deforestation, can intensify these soil conditions. Taurine, a novel growth regulator, holds promise in mediating plant defense responses. Its effects on defense responses are still unclear. Previously, taurine showed potential in improving clover tolerance to alkaline stress and manganese toxicity. Taurine impact on plant growth under Fe deficiency and salinity stress remains uninvestigated. A pot experiment was conducted to evaluate the effects of taurine on pea plant growth, ion uptake, and defense strategies in response to salt stress and Fe deficiency. Iron deficiency was established by substituting 0.1 mM FeSO4 for 0.1 mM Fe-EDTA in the nutrient solution. Salinity stress was induced by incorporating a mixture of NaCl, MgCl2, KCl, Na2SO4, Na2CO3, NaHCO3 and CaCl2 in a 1:1:1:1:1:1:1 ratio to produce a salinity concentration of 100 mM. The simultaneous imposition of salinity and Fe deficiency significantly exacerbated oxidative stress, as evidenced by elevated levels of relative membrane permeability, hydrogen peroxide (H2O2), superoxide radical (O2•-), methylglyoxal (MG), malondialdehyde (MDA), and increased activity of lipoxygenase (LOX). Salinity stress alone and the combination of salinity and Fe deficiency resulted in substantial accumulation of Na+ ions that impeded acquisition of essential nutrients. Taurine (100 and 200 mg L-1) notably improved osmotic adjustment and oxidative defense to diminish water imbalance and oxidative injury in plants under stress. These results suggest that exogenous taurine may serve as a promising means of mitigating the detrimental effects of salt stress and Fe deficiency in plants.


Subject(s)
Iron Deficiencies , Pisum sativum , Humans , Pisum sativum/metabolism , Salinity , Hydrogen Peroxide , Oxidative Stress , Ions , Water , Soil , Antioxidants/metabolism
17.
J Oncol Pharm Pract ; 29(1): 218-225, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35410558

ABSTRACT

INTRODUCTION: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity. CASE REPORT: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis. MANAGEMENT AND OUTCOME: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole. DISCUSSION: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.


Subject(s)
Hypertriglyceridemia , Pancreatitis , Humans , Female , Tamoxifen/adverse effects , Pancreatitis/chemically induced , Pancreatitis/diagnosis , Acute Disease , Hypertriglyceridemia/chemically induced , Gemfibrozil/adverse effects
18.
Phytother Res ; 37(2): 627-644, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36420866

ABSTRACT

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID-19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo-controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg-1 day-1 ) and Nigella sativa seeds (80 mg kg-1 day-1 ) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30-day mortality in the intention-to-treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46-6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76-8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62-7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02-0.92, p = 0.029). No HNS-related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID-19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.


Subject(s)
COVID-19 , Honey , Nigella sativa , Adult , Humans , SARS-CoV-2 , Pakistan/epidemiology , Treatment Outcome
19.
J Appl Clin Med Phys ; 24(11): e14110, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37528747

ABSTRACT

PURPOSE: To develop an angular correction methodology and characterize a high-resolution complementary metal-oxide-semiconductor (CMOS) array for patient specific quality assurance on a robotic arm linear accelerator. METHODS: Beam path files from the treatment planning software (TPS) were used to calculate the angle of radiation beam with respect to the detector plane. Beams from multiple discrete angles were delivered to the CMOS detector array and an angular dependency look up table (LUT) was created. The LUT was then used to correct for the angular dependency of the detector. An iso-centric 5 mm fixed cone, non iso-centric multi-target fixed cone, 10 mm Iris and a multi-leaf collimator (MLC) based collimated plan were delivered to the phantom and compared to the TPS with and without angular correction applied. Additionally, the CMOS array was compared to gafchromic film and a diode array. RESULTS: Large errors of up to 30% were observed for oblique angles. When angular correction was applied, the gamma passing rate increased from 99.2% to 100% (average gamma value decreased from 0.29 to 0.14) for the 5-mm iso-centric cone plan. Similarly, the passing rate increased from 84.0% to 100% for the Iris plan and from 49.98% to 98.4% for the MLC plan when angular correction was applied. For the multi-target plan, applying angular correction improved the gamma passing rate from 94% to 99.6%. The 5 mm iso-centric fixed cone plan was also delivered to film, and the gamma passing rate was 91.3% when using gafchromic film as the reference dataset, whereas the diode array provided insufficient sampling for this plan. CONCLUSION: A methodology of calculating the beam angle based on the beam path files was developed and validated. The array was demonstrated to be superior to other quality assurance tools because of its sub-millimeter spatial resolution and immediate read out of the results.


Subject(s)
Radiosurgery , Radiotherapy, Intensity-Modulated , Robotic Surgical Procedures , Humans , Radiosurgery/methods , Radiometry/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Dosage , Oxides , Quality Assurance, Health Care
20.
Int J Phytoremediation ; 25(5): 630-645, 2023.
Article in English | MEDLINE | ID: mdl-35862619

ABSTRACT

Micro and macro-morphological features contribute to plants' tolerance to a variety of environmental pollutants. The contribution of such structural modifications in the phytoremediation potential of Diplachne fusca populations collected from five saline habitats were explored when treated with 100 to 400 mM NaCl for 75 days along with control. Structural modifications in the populations from the highest salinity included development of aerenchyma in stem instead of chlorenchyma, absence of excretory hairs in stem, and exceptionally large trichomes on the leaf surface to help excretion of excess salt. Large parenchyma cells provided more space for water and solute storage, while broad metaxylem vessels were linked to better conduction water and nutrients, which ultimately excreted via glandular hairs, microhairs, and vesicular hairs. Broad metaxylem vessels and exceptionally long hairs observed in the populations collected from 52 dS m-1. In conclusion, large stem aerenchyma, exceptionally large trichomes on the leaf surface, and tightly packed outer cortical region in roots with intensive sclerification just inside the epidermis accompanied with salt excretion via glandular hairs, microhairs, and vesicular hairs were the main anatomical modifications involved in the phytoremediation potential of D. fusca in hyper-saline environments.


Morpho-anatomical characteristics of the differently adapted populations of Diplachne fusca has never been reported. In particular, structural variation in their mechanism of adaptation for salinity tolerance was investigated for the first time in current study.


Subject(s)
Poaceae , Salt-Tolerant Plants , Biodegradation, Environmental , Sodium Chloride/chemistry , Water , Saline Solution , Salinity
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