Diversity and potential functional role of phyllosphere-associated actinomycetota isolated from cupuassu (Theobroma grandiflorum) leaves: implications for ecosystem dynamics and plant defense strategies.

Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in Theobroma grandiflorum, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches' broom disease caused by Moniliophthora perniciosa. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu's defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability.

Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish.

Although the zebrafish is a major model organism, how they determine sex is not well understood. In domesticated zebrafish, sex determination appears to be polygenic, being influenced by multiple genetic factors that may vary from strain to strain, and additionally can be influenced by environmental factors. However, the requirement of germ cells for female sex determination is well documented: animals that lack germ cells, or oocytes in particular, develop exclusively as males. Recently, it has been determined that oocytes are also required throughout the adult life of the animal to maintain the differentiated female state. How oocytes control sex differentiation and maintenance of the sexual phenotype is unknown. We therefore generated targeted mutations in genes for two oocyte produced signaling molecules, Bmp15 and Gdf9 and here report a novel role for Bmp15 in maintaining adult female sex differentiation in zebrafish. Females deficient in Bmp15 begin development normally but switch sex during the mid- to late- juvenile stage, and become fertile males. Additionally, by generating mutations in the aromatase cyp19a1a, we show that estrogen production is necessary for female development and that the function of Bmp15 in female sex maintenance is likely linked to the regulation of estrogen biosynthesis via promoting the development of estrogen-producing granulosa cells in the oocyte follicle.

DNA Adduct Formation in the Lungs and Brain of Rats Exposed to Low Concentrations of [13C2]-Acetaldehyde.

Air pollution is a major environmental risk for human health. Acetaldehyde is present in tobacco smoke and vehicle exhaust. In this study, we show that [13C2]-acetaldehyde induces DNA modification with the formation of isotopically labeled 1, N2-propano-2'-deoxyguanosine adducts in the brain and lungs of rats exposed to concentrations of acetaldehyde found in the atmosphere of megacities. The adduct, with the addition of two molecules of isotopically labeled acetaldehyde [13C4]-1, N2-propano-dGuo, was detected in the lung and brain tissues of exposed rats by micro-HPLC/MS/MS. Structural confirmation of the products was unequivocally performed by nano-LC/ESI+-HRMS3 analyses. DNA modifications induced by acetaldehyde have been regarded as a key factor in the mechanism of mutagenesis and may be involved in the cancer risks associated with air pollution.

Biotechnological potential of plant growth-promoting bacteria from the roots and rhizospheres of endemic plants in ironstone vegetation in southeastern Brazil.

Microorganisms associated with plants have a great biotechnological potential, but investigations of these microorganisms associated with native plants in peculiar environments has been incipient. The objective of this study was to analyze the plant growth-promoting bacteria potential of cultivable bacteria associated with rare plants from the ferruginous rocky fields of the Brazilian Iron Quadrangle. The roots and rhizospheres of nine endemic plants species and samples of a root found in a lateritiric duricrust (canga) cave were collected, the culturable bacteria isolated and prospected for distinct biotechnological and ecological potentials. Out of the 148 isolates obtained, 8 (5.4%) showed potential to promote plant growth, whereas 4 (2.7%) isolates acted as biocontrol agents against Xanthomonas citri pathotype A (Xac306), reducing the cancrotic lesions by more than 60% when co-inoculated with this phytopathogen in Citrus sinensis plants. Moreover, other 4 (2.7%) isolates were classified as potential bioremediation agents, being able to withstand high concentrations of arsenite (5 mM As3+) and arsenate (800 mM As5+), by removing up to 35% and 15% of this metalloid in solution, respectively. These same four isolates had a positive influence on the growth of both the roots and the aerial parts when inoculated with tomato seeds in the soil contaminated with arsenic. This is the first time that an investigation highlights the potentialities of bacteria associated with rare plants of ferruginous rocky fields as a reservoir of microbiota of biotechnological and ecological interest, highlighting the importance of conservation of this area that is undergoing intense anthropic activity.

Association Between Proton Pump Inhibitors and Microscopic Colitis.

OBJECTIVE: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. DATA SOURCES: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. STUDY SELECTION: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. DATA EXTRACTION/SYNTHESIS: A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. CONCLUSIONS: There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

Zebrafish Germ Cell Tumors.

Germ cell tumors (GCTs) are malignant cancers that arise from embryonic precursors known as Primordial Germ Cells. GCTs occur in neonates, children, adolescents and young adults and can occur in the testis, the ovary or extragonadal sites. Because GCTs arise from pluripotent cells, the tumors can exhibit a wide range of different histologies. Current cisplatin-based combination therapies cures most patients, however at the cost of significant toxicity to normal tissues. While GWAS studies and genomic analysis of human GCTs have uncovered somatic mutations and loci that might confer tumor susceptibility, little is still known about the exact mechanisms that drive tumor development, and animal models that faithfully recapitulate all the different GCT subtypes are lacking. Here, we summarize current understanding of germline development in humans and zebrafish, describe the biology of human germ cell tumors, and discuss progress and prospects for zebrafish GCT models that may contribute to better understanding of human GCTs.

JUN mRNA translation regulation is mediated by multiple 5' UTR and start codon features.

Regulation of mRNA translation by eukaryotic initiation factors (eIFs) is crucial for cell survival. In humans, eIF3 stimulates translation of the JUN mRNA which encodes the transcription factor JUN, an oncogenic transcription factor involved in cell cycle progression, apoptosis, and cell proliferation. Previous studies revealed that eIF3 activates translation of the JUN mRNA by interacting with a stem loop in the 5' untranslated region (5' UTR) and with the 5' -7-methylguanosine cap structure. In addition to its interaction site with eIF3, the JUN 5' UTR is nearly one kilobase in length, and has a high degree of secondary structure, high GC content, and an upstream start codon (uAUG). This motivated us to explore the complexity of JUN mRNA translation regulation in human cells. Here we find that JUN translation is regulated in a sequence and structure-dependent manner in regions adjacent to the eIF3-interacting site in the JUN 5' UTR. Furthermore, we identify contributions of an additional initiation factor, eIF4A, in JUN regulation. We show that enhancing the interaction of eIF4A with JUN by using the compound Rocaglamide A (RocA) represses JUN translation. We also find that both the upstream AUG (uAUG) and the main AUG (mAUG) contribute to JUN translation and that they are conserved throughout vertebrates. Our results reveal additional layers of regulation for JUN translation and show the potential of JUN as a model transcript for understanding multiple interacting modes of translation regulation.

Prevalence of microplastics in Peruvian mangrove sediments and edible mangrove species.

Mangrove ecosystems have been hypothesised as a potential sink of microplastic debris, which could pose a threat to mangrove biota and ecological function. In this field-study we establish the prevalence of microplastics in sediments and commercially-exploited Anadara tuberculosa (black ark) and Ucides occidentalis (mangrove crab) from five different zones in the mangrove ecosystem of Tumbes, Peru. Microplastic were evident in all samples, with an average of 726 ± 396 microplastics/kg for the sediment, although no differences between the different zones of the mangrove ecosystem were observed. Microplastic concentrations were 1.6± 1.1 items/g for the black ark and 1.9 ± 0.9 microplastics/g for the mangrove crab, with a difference in the microplastic abundance between species (p < 0.05), and between the gills and stomachs of the crab (p < 0.01). Human intake of microplastics from these species, for the population in Tumbes, is estimated at 431 items per capita per year. The outcomes of this work highlight that the mangrove ecosystem is widely contaminated with microplastics, presenting a concern for the marine food web and food security.

In vivo AAV-SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy.

Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased functional mapping of tumor-infiltrating NK (TINK) cells using in vivo adeno-associated virus (AAV)-SB (Sleeping Beauty)-CRISPR (clustered regularly interspaced short palindromic repeats) screens in four solid tumor mouse models. In parallel, we characterized single-cell transcriptomic landscapes of TINK cells, which identified previously unexplored subpopulations of NK cells and differentially expressed TINK genes. As a convergent hit, CALHM2-knockout (KO) NK cells showed enhanced cytotoxicity and tumor infiltration in mouse primary NK cells and human chimeric antigen receptor (CAR)-NK cells. CALHM2 mRNA reversed the CALHM2-KO phenotype. CALHM2 KO in human primary NK cells enhanced their cytotoxicity, degranulation and cytokine production. Transcriptomics profiling revealed CALHM2-KO-altered genes and pathways in both baseline and stimulated conditions. In a solid tumor model resistant to unmodified CAR-NK cells, CALHM2-KO CAR-NK cells showed potent in vivo antitumor efficacy. These data identify endogenous genetic checkpoints that naturally limit NK cell function and demonstrate the use of CALHM2 KO for engineering enhanced NK cell-based immunotherapies.

Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging.

BACKGROUND: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac. METHODS: Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women. RESULTS: ChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women. CONCLUSIONS: This study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Elevated α-methyl-γ-hydroxy-1,N2-propano-2'-deoxyguanosine levels in urinary samples from individuals exposed to urban air pollution.

Acetaldehyde and crotonaldehyde are genotoxic aldehydes present in tobacco smoke and vehicle exhaust. The reaction of these aldehydes with 2'-deoxyguanosine in DNA produces α-methyl-γ-hydroxy-1,N(2)-propano-2'-deoxyguanosine (1,N(2)-propanodGuo). Online HPLC-tandem mass spectrometry was utilized to accurately quantify 1,N(2)-propanodGuo in human urinary samples from 47 residents of São Paulo City (SP) and 35 residents of the rural municipality of São João da Boa Vista (SJBV) in the state of São Paulo. Significantly higher 1,N(2)-propanodGuo levels were found in the samples from SP donors than in samples from SJBV donors. Our results provide the first evidence that elevated levels of 1,N(2)-propanodGuo in urinary samples may be correlated with urban air pollution.

Bio-Mapping of Microbial Indicators and Pathogen Quantitative Loads in Commercial Broiler Processing Facilities in South America.

A bio-mapping study was conducted with the aim of creating a microbiological baseline on indicator organisms and pathogens in commercial broiler processing facilities located in a country in South America. Whole chicken carcass and wing rinses were collected from five stages of the poultry processing line: live receiving (LR), rehanger (R), post-evisceration (PE), post-chilling (PC), and wings (W). Rinses (n = 150) were enumerated using the MicroSnap™ system for total viable counts (TVC) and Enterobacteriaceae (EB), while the BAX®-System-SalQuant® and BAX®-System-CampyQuant™ were used for Salmonella and Campylobacter, respectively. TVC and EB were significantly different between stages at the processing line (p < 0.01). There was a significant reduction from LR to PC for both microbial indicators. TVC and EB counts increased significantly from PC to W. Salmonella counts at PC were significantly different from the other stages at the processing line (p = 0.03). Campylobacter counts were significantly higher than the other stages at PC (p < 0.01). The development of bio-mapping baselines with microbial indicators showed consistent reduction up to the post-chilling stage, followed by an increase at the wings sampling location. The quantification of pathogens demonstrates that prevalence analysis as a sole measurement of food safety is not sufficient to evaluate the performance of processing operations and sanitary dressing procedures in commercial processing facilities.

JUN mRNA Translation Regulation is Mediated by Multiple 5' UTR and Start Codon Features.

Regulation of mRNA translation by eukaryotic initiation factors (eIFs) is crucial for cell survival. In humans, eIF3 stimulates translation of the JUN mRNA which encodes the transcription factor JUN, an oncogenic transcription factor involved in cell cycle progression, apoptosis, and cell proliferation. Previous studies revealed that eIF3 activates translation of the JUN mRNA by interacting with a stem loop in the 5' untranslated region (5' UTR) and with the 5'-7-methylguanosine cap structure. In addition to its interaction site with eIF3, the JUN 5' UTR is nearly one kilobase in length, and has a high degree of secondary structure, high GC content, and an upstream start codon (uAUG). This motivated us to explore the complexity of JUN mRNA translation regulation in human cells. Here we find that JUN translation is regulated in a sequence and structure-dependent manner in regions adjacent to the eIF3-interacting site in the JUN 5' UTR. Furthermore, we identify contributions of an additional initiation factor, eIF4A, in JUN regulation. We show that enhancing the interaction of eIF4A with JUN by using the compound Rocaglamide A (RocA) represses JUN translation. We also find that both the upstream AUG (uAUG) and the main AUG (mAUG) contribute to JUN translation and that they are conserved throughout vertebrates. Our results reveal additional layers of regulation for JUN translation and show the potential of JUN as a model transcript for understanding multiple interacting modes of translation regulation.

Isolation and Annotation of Xitlalli, a Cluster EK1 Actinobacteriophage Isolated Using Microbacterium foliorum.

Xitlalli is an actinobacteriophage that was isolated from soil using Microbacterium foliorum. Based on gene content similarity to phages in the Actinobacteriophage Database, Xitlalli is assigned to cluster EK1. The genome is 53,929 bp long and contains 52 protein-coding genes, of which 26% could be assigned functions.

Perturbomics of tumor-infiltrating NK cells.

Natural killer (NK) cells are an innate immune cell type that serves at the first level of defense against pathogens and cancer. NK cells have clinical potential, however, multiple current limitations exist that naturally hinder the successful implementation of NK cell therapy against cancer, including their effector function, persistence, and tumor infiltration. To unbiasedly reveal the functional genetic landscape underlying critical NK cell characteristics against cancer, we perform perturbomics mapping of tumor infiltrating NK cells by joint in vivo AAV-CRISPR screens and single cell sequencing. We establish a strategy with AAV-SleepingBeauty(SB)- CRISPR screening leveraging a custom high-density sgRNA library targeting cell surface genes, and perform four independent in vivo tumor infiltration screens in mouse models of melanoma, breast cancer, pancreatic cancer, and glioblastoma. In parallel, we characterize single-cell transcriptomic landscapes of tumor-infiltrating NK cells, which identifies previously unexplored sub-populations of NK cells with distinct expression profiles, a shift from immature to mature NK (mNK) cells in the tumor microenvironment (TME), and decreased expression of mature marker genes in mNK cells. CALHM2, a calcium homeostasis modulator that emerges from both screen and single cell analyses, shows both in vitro and in vivo efficacy enhancement when perturbed in chimeric antigen receptor (CAR)-NK cells. Differential gene expression analysis reveals that CALHM2 knockout reshapes cytokine production, cell adhesion, and signaling pathways in CAR- NKs. These data directly and systematically map out endogenous factors that naturally limit NK cell function in the TME to offer a broad range of cellular genetic checkpoints as candidates for future engineering to enhance NK cell-based immunotherapies.

Virulence factors of the genus Fusarium with targets in plants.

Fusarium spp. comprise various species of filamentous fungi that cause severe diseases in plant crops of both agricultural and forestry interest. These plant pathogens produce a wide range of molecules with diverse chemical structures and biological activities. Genetic functional analyses of some of these compounds have shown their role as virulence factors (VF). However, their mode of action and contributions to the infection process for many of these molecules are still unknown. This review aims to analyze the state of the art in Fusarium VF, emphasizing their biological targets on the plant hosts. It also addresses the current experimental approaches to improve our understanding of their role in virulence and suggests relevant research questions that remain to be answered with a greater focus on species of agroeconomic importance. In this review, a total of 37 confirmed VF are described, including 22 proteinaceous and 15 non-proteinaceous molecules, mainly from Fusarium oxysporum and Fusarium graminearum and, to a lesser extent, in Fusarium verticillioides and Fusarium solani.

Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence.

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.

Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects.

BACKGROUND: Neural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. METHODS: A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case-control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. RESULTS: Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003-0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. CONCLUSIONS: To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.

Nephrotic Syndrome in Adult Patients With COVID-19 Infection or Post COVID-19 Vaccine: A Systematic Review.

Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.