ABSTRACT
BACKGROUND: Despite evidence showing a connection between inflammation and endometrial cancer (EC) risk, the surveys on genetic correlation and cohort studies investigating the impact on long-term outcomes have yet to be refined. We aimed to address the impact of inflammation factors on the pathogenesis, progression and consequences of EC. METHODS: For the genetic correlation analyses, a two-sample of Mendelian randomization (MR) study was applied to investigate inflammation-related single-nucleotide polymorphisms involved with endometrial cancer from GWAS databases. The observational retrospective study included consecutive patients diagnosed with EC (stage I to IV) with surgeries between January 2010 and October 2020 at the Cancer Hospital of Shantou University Medical College. RESULTS: The 2-sample MR surveys indicated no causal relationship between inflammatory cytokines and endometrial cancer. 780 cases (median age, 55.0 years ) diagnosed with EC were included in the cohort and followed up for an average of 6.8 years. Increased inflammatory parameters at baseline were associated with a higher FIGO stage and invasive EC risk (odds ratios [OR] 1.01 to 4.20). Multivariate-cox regression suggested that multiple inflammatory indicators were significantly associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Nomogram models based on inflammatory risk and clinical factors were developed for OS and PFS with C-index of 0.811 and 0.789, respectively. LASSO regression for the validation supported the predictive efficacy of inflammatory and clinical factors on the long-term outcomes of EC. CONCLUSIONS: Despite the fact that the genetic surveys did not show a detrimental impact of inflammatory cytokines on the endometrial cancer risk, our cohort study suggested that inflammatory level was associated with the progression and long-term outcomes of EC. This evidence may contribute to new strategies targeted at decreasing inflammation levels during EC therapy.
Subject(s)
Endometrial Neoplasms , Genome-Wide Association Study , Inflammation , Polymorphism, Single Nucleotide , Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Middle Aged , Inflammation/genetics , Retrospective Studies , Aged , Mendelian Randomization Analysis , Nomograms , Cohort Studies , Adult , PrognosisABSTRACT
Trichomonas vaginalis and Mycoplasma hominis, two microorganisms causing infections of the urogenital tract, are closely associated in that they establish an endosymbiosis relationship, the only case among human pathogens. As a result, the presence of one microorganism may be considered a sign that the other is present as well. Identification of the two pathogens in clinical samples is based on cultivation techniques on specific media, even though in recent years, new sensitive and rapid molecular techniques have become. Here, we demonstrate that the concomitant presence of T.vaginalis in urogenital swabs may lead to a delay in the identification of M.hominis, and thus to an underestimation of bacterial infections when cultural techniques are used.
Subject(s)
Mycoplasma Infections , Mycoplasma hominis , Trichomonas vaginalis , Mycoplasma hominis/isolation & purification , Mycoplasma hominis/genetics , Trichomonas vaginalis/isolation & purification , Trichomonas vaginalis/genetics , Humans , Mycoplasma Infections/microbiology , Female , Trichomonas Vaginitis/microbiology , Trichomonas Vaginitis/parasitology , Trichomonas Vaginitis/diagnosis , Male , Sensitivity and Specificity , Urogenital System/microbiology , Urogenital System/parasitology , AdultABSTRACT
The SARS-CoV-2 BF.7 variant represents one of the most recent subvariant under monitoring. At the beginning of the 2023 it caused several concerns especially in Asia because of a resurge in COVID-19 cases. Here we perform a genome-based integrative approach on SARS-CoV-2 BF.7 to shed light on this emerging lineage and produce some consideration on its real dangerousness. Both genetic and structural data suggest that this new variant currently does not show evidence of an high expansion capability. It is very common in Asia, but it appears less virulent than other Omicron variants as proved by its relatively low evolutionary rate (5.62 × 10-4 subs/sites/years). The last plateau has been reached around December 14, 2022 and then the genetic variability, and thus the viral population size, no longer increased. As already seen for several previous variants, the features that may be theoretically related to advantages are due to genetic drift that allows to the virus a constant adaptability to the host, but is not strictly connected to a fitness advantage. These results have further pointed that the genome-based monitoring must continue uninterruptedly to be prepared and well documented on the real situation.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Asia/epidemiology , Biological EvolutionABSTRACT
The severe acute respiratory syndrome coronavirus 2 EG.5 lineage is the latest variant under monitoring, and it is generating significant concern due to its recent upward trend in prevalence. Our aim was to gain insights into this emerging lineage and offer insights into its actual level of threat. Both genetic and structural data indicate that this novel variant presently lacks substantial evidence of having a high capacity for widespread transmission. Their viral population sizes expanded following a very mild curve and peaked several months after the earliest detected sample. Currently, neither the viral population size of EG.5 nor that of its first descendant is increasing. The genetic variability appear to be flattened, as evidenced by its relatively modest evolutionary rate (9.05 × 10-4 subs/site/year). As has been observed with numerous prior variants, attributes that might theoretically provide advantages seem to stem from genetic drift, enabling the virus to continually adjust to its host, albeit without a clear association with enhanced dangerousness. These findings further underscore the necessity for ongoing genome-based monitoring, ensuring preparedness and a well-documented understanding of the unfolding situation.
Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Biological Evolution , Genetic Drift , Population DensityABSTRACT
Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Bayes Theorem , Spike Glycoprotein, Coronavirus/chemistryABSTRACT
The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10-4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages.
Subject(s)
COVID-19 , Humans , Bayes Theorem , COVID-19/genetics , SARS-CoV-2/genetics , Genetic DriftABSTRACT
Trichomonas vaginalis is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in T. vaginalis L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors.
Subject(s)
Rhamnose , Trichomonas vaginalis , Female , Humans , Rhamnose/chemistry , Biosynthetic Pathways , Glucose , Hydro-Lyases/metabolism , Uridine Diphosphate/metabolismABSTRACT
The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10-4 and 7 × 10-4 subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.
Subject(s)
COVID-19 , Humans , Bayes Theorem , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2/genetics , Biological EvolutionABSTRACT
Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.
Subject(s)
Host-Parasite Interactions , Oncolytic Virotherapy/methods , Parasites/virology , Parasitic Diseases/therapy , Phage Therapy/methods , Animals , Humans , Oncolytic Virotherapy/standards , Phage Therapy/standardsABSTRACT
Mycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extragenital conditions. Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated with virulence. The current study focused on investigating the role of MHO_0730 as a virulence factor and demonstrated that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection, acting both as a nuclease with its amino acidic portion and as a potent inducer of Neutrophil extracellular trapsosis with its N-terminal lipid moiety. Evidence for M. hominis neutrophil extracellular trap escape is also presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity and provide additional knowledge on M. hominis virulence and survival in the host.
Subject(s)
Bacterial Proteins/metabolism , Extracellular Traps/immunology , Extracellular Traps/metabolism , Host-Pathogen Interactions/immunology , Mycoplasma Infections/immunology , Mycoplasma Infections/microbiology , Mycoplasma hominis/physiology , Humans , Lipoproteins/metabolism , Mycoplasma Infections/metabolism , Mycoplasma hominis/enzymology , Neutrophils/immunology , Neutrophils/metabolism , Protein Transport , Recombinant Proteins , VirulenceSubject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Mutation , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
Trichomonas vaginalis is an anaerobic protist, responsible for the most prevalent non-viral sexually transmitted infection in humans. One of the most intriguing aspects of T. vaginalis pathobiology is the complex relationship with intracellular microbial symbionts: a group of dsRNA viruses belonging to family of Totiviridae (T. vaginalis virus), and eubacteria belonging to the Mycoplasma genus, in particular Mycoplasma hominis. Both microorganisms seem to strongly influence the lifestyle of T. vaginalis, suggesting a role of the symbiosis in the high variability of clinical presentation and sequelae during trichomoniasis. In the last few years many aspects of this unique symbiotic relationship have been investigated: M. hominis resides and replicates in the protozoan cell, and T. vaginalis is able to pass the bacterial infection to both mycoplasma-free protozoan isolates and human epithelial cells; M. hominis synergistically upregulates the proinflammatory response of human monocytes to T. vaginalis. Furthermore, the influence of M. hominis over T. vaginalis metabolism and physiology has been characterized. The identification of a novel species belonging to the class of Mollicutes (Candidatus Mycoplasma girerdii) exclusively associated to T. vaginalis opens new perspectives in the research of the complex series of events taking place in the multifaceted world of the vaginal microbiota, both under normal and pathological conditions.
Subject(s)
Mycoplasma Infections/microbiology , Mycoplasma hominis/physiology , Symbiosis , Trichomonas Vaginitis/parasitology , Trichomonas vaginalis/pathogenicity , Female , Humans , Inflammation , Microbiota , Mycoplasma hominis/immunology , Sexually Transmitted Diseases/immunology , Sexually Transmitted Diseases/parasitology , Totiviridae/metabolism , Trichomonas vaginalis/immunology , Vagina/microbiology , Vagina/parasitologyABSTRACT
The flagellated protozoon Trichomonas vaginalis, responsible for trichomoniasis, can establish a symbiotic relationship with the bacterium Mycoplasma hominis and can harbor double-stranded RNA Trichomonasvirus (TVV). In this study, we investigated by real-time PCR the prevalence of the four TVVs and of M. hominis among 48 T. vaginalis strains isolated in Italy, and we evaluated a possible association with metronidazole resistance. Fifty percent of the analyzed trichomonad strains tested positive for at least one TVV T. vaginalis, with TVV2 being the most prevalent, followed by TVV1 and TVV3. Two T. vaginalis strains were infected by TVV4, detected in Europe for the first time. Interestingly, we found more than one TVV species in 75% of positive trichomonad strains. M. hominis was present in 81.25% of T. vaginalis isolates tested, and no statistically significant association was observed with the infection by any TVV. Metronidazole sensitivity of T. vaginalis isolates was evaluated in vitro, and no correlation was observed between minimal lethal concentration and the presence of TVVs. This is the first report on TVV infection of T. vaginalis in Italy. Even if no association of TVV positive isolates with the presence of the symbiont M. hominis or with metronidazole resistance was observed, further studies are needed to shed light on the effective role of infecting microorganisms on the pathophysiology of T. vaginalis.
Subject(s)
Mycoplasma hominis/isolation & purification , RNA Viruses/isolation & purification , Trichomonas vaginalis/microbiology , Trichomonas vaginalis/virology , Antiprotozoal Agents/pharmacology , Drug Resistance , Humans , Italy , Metronidazole/pharmacology , Mycoplasma hominis/classification , Mycoplasma hominis/genetics , Mycoplasma hominis/physiology , Prevalence , RNA Viruses/classification , RNA Viruses/genetics , RNA Viruses/physiology , RNA, Double-Stranded/genetics , RNA, Viral/genetics , Symbiosis , Trichomonas Infections/parasitology , Trichomonas vaginalis/drug effects , Trichomonas vaginalis/physiologyABSTRACT
The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.
Subject(s)
Macrophages/immunology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/parasitology , Protozoan Proteins/immunology , Trichomonas Infections/immunology , Trichomonas vaginalis/immunology , Amino Acid Sequence , Cell Line, Tumor , Cells, Cultured , Conserved Sequence , Humans , Intramolecular Oxidoreductases/genetics , Intramolecular Oxidoreductases/immunology , MAP Kinase Signaling System/immunology , Macrophage Migration-Inhibitory Factors/genetics , Macrophage Migration-Inhibitory Factors/immunology , Macrophages/cytology , Macrophages/parasitology , Male , Molecular Sequence Data , Prostate/immunology , Prostate/parasitology , Prostate/pathology , Prostatic Neoplasms/pathology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Sequence Homology , Trichomonas Infections/complications , Trichomonas Infections/parasitology , Trichomonas vaginalis/genetics , Trichomonas vaginalis/metabolismABSTRACT
Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response.
Subject(s)
Acanthamoeba castellanii/immunology , Amebiasis/immunology , Cytokines/metabolism , Interleukin-10/metabolism , Leukocytes, Mononuclear/metabolism , Macrophages/metabolism , Analysis of Variance , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Genotype , HumansABSTRACT
OBJECTIVES: Persistence of antibodies against pathogens after antimicrobial treatment is a marker of therapy failure or evolution to a chronic infection. The kinetics of antibody production decrease following antigen elimination is highly variable, and predicting the duration of soluble immunity in infectious diseases is often impossible. This hampers the development and use of immunoassays for diagnostic and seroepidemiological purposes. In the case of Trichomonas vaginalis infection, the kinetics of antibody levels decrease following therapy has never been studied. We thus investigated the clearance of circulating anti-T. vaginalis IgGs after pharmacological treatment in patients affected by trichomoniasis. METHODS: 18 female patients affected by acute trichomoniasis were enrolled in this study. After metronidazole therapy administration, subjects were followed up monthly up to 5â months, and serum levels of anti-T. vaginalis IgGs were measured by ELISA. RESULTS: We showed that a successful therapy is characterised by a relatively fast decline of specific antibodies, until turning into negative by ELISA in 1-3â months. In a few patients we observed that the persistence of anti-T. vaginalis antibodies was associated with an evolution to chronic infection, which may be due to treatment failure or to reinfection by untreated sexual partners. CONCLUSIONS: Our results describe the direct correlation between the decline of a specific humoral anti-T. vaginalis response and an effective antimicrobial therapy. These findings may facilitate the follow-up approach to circumvent limitations in developing new diagnostic tools and techniques routinely used in microbiology laboratories to assess the presence of T. vaginalis in clinical samples.
Subject(s)
Antibodies, Protozoan/blood , Antiprotozoal Agents/therapeutic use , Metronidazole/therapeutic use , Trichomonas Infections/diagnosis , Trichomonas vaginalis/immunology , Vagina/parasitology , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Kinetics , Treatment Outcome , Trichomonas Infections/drug therapy , Trichomonas Infections/immunology , Trichomonas vaginalis/pathogenicityABSTRACT
Background: The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. Methods: We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. Results: IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Conclusion: Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. Declaration: This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.
Subject(s)
Diarrhea, Infantile , Facies , Fetal Growth Retardation , Gastrointestinal Microbiome , Hair Diseases , Polycystic Ovary Syndrome , Female , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Polycystic Ovary Syndrome/geneticsABSTRACT
OBJECTIVE: The current study aimed to address and rank which exercise-based interventions are preferable to standard care/no therapy or another exercise intervention for postpartum depression (PPD) management and provide estimates for future definitive evidence. METHODS: The authors systematically searched PubMed, Embase, the Web of Science, PsycInfo, and ClinicalTrails.gov for randomized controlled trials (RCTs) on exercise-based interventions for PPD from their inception to May 9, 2023. Included were RCTs of exercise-based interventions for PPD with at least 4 weeks' duration. The pooled effects of intervention comparisons were generated by the Bayesian random-effects model, and the quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: Twelve RCTs (1260 women; mean age, 20-35 years) comparing exercise-based interventions with usual care/no therapy were included. Exercise effectively treats depressive symptoms (standard mean difference [SMD], -0.81 [95% confidence interval (CI), -1.20 to -0.42], P < 0.001). Pram walking was significantly associated with a reduction of depressive symptoms during the postpartum period (SMD, -1.00 [95% CI, -2.60 to -0.10], P = 0.020), as well as yoga (SMD, -0.73 [95% CI, -1.84 to -0.43], P < 0.001) and supervised mixed exercise (SMD, -0.77 [95% CI, -1.67 to -0.01], P = 0.041) compared with usual care/no therapy. In indirect comparisons, pram walking (surface under the cumulative ranking curve, 58.9%) was better than yoga (SMD, -0.28 [95% CI, -1.86 to 1.22], P = 0.322) and supervised mixed exercise (SMD, -0.23 [95% CI, -1.59 to 1.12], P = 0.358). However, the difference was not statistically significant. The confidence in evidence was very low to moderate. CONCLUSION: In women with PPD, all commonly prescribed physical exercises were effective alternative or complementary treatments. However, pram walking may perform better in improving the symptoms of PPD.
Subject(s)
Depression, Postpartum , Quality of Life , Female , Humans , Young Adult , Adult , Depression, Postpartum/therapy , Network Meta-Analysis , Exercise , Depression/therapyABSTRACT
The cultivation of cyanobacteria by exploiting available in situ resources represents a possible way to supply food and oxygen to astronauts during long-term crewed missions on Mars. Here, we evaluated the possibility of cultivating the extremophile cyanobacterium Chroococcidiopsis thermalis CCALA 050 under operating conditions that should occur within a dome hosting a recently patented process to produce nutrients and oxygen on Mars. The medium adopted to cultivate this cyanobacterium, named Martian medium, was obtained using a mixture of regolith leachate and astronauts' urine simulants that would be available in situ resources whose exploitation could reduce the mission payload. The results demonstrated that C. thermalis can grow in such a medium. For producing high biomass, the best medium consisted of specific percentages (40%vol) of Martian medium and a standard medium (60%vol). Biomass produced in such a medium exhibits excellent antioxidant properties and contains significant amounts of pigments. Lipidomic analysis demonstrated that biomass contains strategic lipid classes able to help the astronauts facing the oxidative stress and inflammatory phenomena taking place on Mars. These characteristics suggest that this strain could serve as a valuable nutritional resource for astronauts.