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Microbial Biotechnology Jul 2024Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome... (Review)
Review
Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome and immune system maturation. As a result, breastfeeding can impact infant health from infancy, through adolescence, and into adulthood. From protecting the infant from infections, to reducing the risk of obesity, type 1 diabetes and childhood leukaemia, many positive health outcomes are observed in infants receiving breastmilk. For the mother, breastfeeding protects against postpartum bleeding and depression, increases weight loss, and long-term lowers the risk of type 2 diabetes, breast and ovarian cancer, and cardiovascular diseases. Beyond infants and mothers, the wider society is also impacted because of avoidable costs relating to morbidity and mortality derived from a lack of human milk exposure. In this review, Medline was used to search for relevant articles to discuss the health benefits of breastfeeding and its societal impact before exploring future recommendations to enhance our understanding of the mechanisms behind breastfeeding's positive effects and promote breastfeeding on a global scale.
Topics: Humans; Breast Feeding; Infant; Milk, Human; Female; Infant, Newborn
PubMed: 38946112
DOI: 10.1111/1751-7915.14520 -
Gene Jun 2024Primary ovarian insufficiency (POI) affects around 2-4% of women before the age of 40. Genetic factors play an important role in POI. The GDF9 gene has been identified...
BACKGROUND
Primary ovarian insufficiency (POI) affects around 2-4% of women before the age of 40. Genetic factors play an important role in POI. The GDF9 gene has been identified as a significant genetic contributor of POI. However, the pathogenicity and penetrance of GDF9 variants remain uncertain.
METHODS
A next-generation sequencing approach was employed to investigate the entire coding region of the GDF9 gene in a cohort of 1281 patients with POI or diminished ovarian reserve (DOR). The frequency of each identified GDF9 variant was then compared with that of the general population, taking into account the ethnicity of each individual.
RESULTS
By screening the entire coding region of the GDF9 gene, we identified 19 different variants, including 1 pathogenic frameshift variant. In total, 36 patients with POI/DOR (2.8%) carried at least one GDF9 variant. With regard to missense variants, no significant overrepresentation of the most common variants was observed in our POI/DOR cohort in comparison to the general or specific ethnic subgroups. Only one homozygous subject had a frameshift loss of function variant.
CONCLUSION
This epidemiological study suggests that the vast majority of heterozygous missense variants could be considered as variants of uncertain significance and the homozygous loss-of-function variant could be considered as a pathogenic variant. The identification of a novel case of a homozygous POI patient with a heterozygous mother carrying the same variant with normal ovarian function strongly suggests that GDF9 syndrome is an autosomal recessive disorder.
PubMed: 38942181
DOI: 10.1016/j.gene.2024.148734 -
Reviews in Medical Virology Jul 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019 and rapidly became a pandemic as coronavirus disease 2019 (COVID-19). Apart... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019 and rapidly became a pandemic as coronavirus disease 2019 (COVID-19). Apart from other organs, presence of specific receptor angiotensin-converting enzyme (ACE2) and corresponding proteases such as transmembrane serine protease 2, basigin and cysteine protease cathepsin L make follicular somatic cells as well as oocyte as potential targets for SARS-CoV-2 infection. The SARS-CoV-2 causes inflammation and hypoxia that generate reactive oxygen species (ROS) in critically ill patients. In addition, a large number of casualties and insecurity of life due to repeated waves of SARS-CoV-2 infection generate psychological stress and cortisol resulting in the further generation of ROS. The excess levels of ROS under physiological range cause meiotic instability, while high levels result in oxidative stress that trigger various death pathways and affect number as well as quality of follicular oocytes. Although, emerging evidence suggests that the SARS-CoV-2 utilises cellular machinery of ovarian follicular cells, generates ROS and impairs quality of follicular oocytes, the underlying mechanism of viral entry into host cell and its negative impact on the follicular oocyte remains poorly understood. Therefore, this review summarises emerging evidence on the presence of cellular machinery for SARS-CoV-2 in ovarian follicles and the potential negative impact of viral infection on the follicular oocytes that affect ovarian functions in critically ill and stressed women.
Topics: Humans; COVID-19; SARS-CoV-2; Female; Oocytes; Angiotensin-Converting Enzyme 2; Reactive Oxygen Species; Virus Internalization; Cathepsin L; Basigin; Ovarian Follicle; Oxidative Stress; Serine Endopeptidases
PubMed: 38937111
DOI: 10.1002/rmv.2568 -
In Vivo (Athens, Greece) 2024Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping...
Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.
BACKGROUND/AIM
Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA.
PATIENTS AND METHODS
Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed.
RESULTS
Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up.
CONCLUSION
Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.
Topics: Humans; Female; Ovarian Neoplasms; Middle Aged; Uterine Cervical Neoplasms; Adult; Diagnosis, Differential; Carcinoma, Endometrioid; Adenocarcinoma, Mucinous; Papillomavirus Infections; Aged; Adenocarcinoma; Papillomaviridae; Neoplasm Metastasis; Human Papillomavirus Viruses
PubMed: 38936897
DOI: 10.21873/invivo.13654 -
Viruses Jun 2024Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges...
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis and psoriasis and is recognized for its anti-cancer properties and has been shown to enhance both VSVΔ51 and HSV-1 oncolytic activity. Tepilamide fumarate (TPF) is a DMF analog currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis. The aim of this study was to evaluate the potential of TPF in enhancing the effectiveness of oncolytic viruses. In vitro, TPF treatment rendered 786-0 carcinoma cells more susceptible to VSVΔ51 infection, leading to increased viral replication. It outperformed DMF in both increasing viral infection and increasing the killing of these resistant cancer cells and other cancer cell lines tested. Ex vivo studies demonstrated TPF's selective boosting of oncolytic virus infection in cancer cells without affecting healthy tissues. Effectiveness was notably high in pancreatic and ovarian tumor samples. Our study further indicates that TPF can downregulate the IFN pathway through a similar mechanism to DMF, making resistant cancer cells more vulnerable to viral infection. Furthermore, TPF's impact on gene therapy was assessed, revealing its ability to enhance the transduction efficiency of vectors such as lentivirus, adenovirus type 5, and adeno-associated virus type 2 across various cell lines. This data underscore TPF's potential role in not only oncolytic virotherapy but also in the broader application of gene therapy. Collectively, these findings position TPF as a promising agent in oncolytic virotherapy, warranting further exploration of its therapeutic potential.
Topics: Humans; Oncolytic Virotherapy; Cell Line, Tumor; Oncolytic Viruses; Virus Replication; Fumarates; Neoplasms; Dimethyl Fumarate; Herpesvirus 1, Human
PubMed: 38932212
DOI: 10.3390/v16060920 -
Microorganisms May 2024Some infectious agents have the potential to cause specific modifications in the cellular microenvironment that could be propitious to the carcinogenesis process.... (Review)
Review
Some infectious agents have the potential to cause specific modifications in the cellular microenvironment that could be propitious to the carcinogenesis process. Currently, there are specific viruses and bacteria, such as human papillomavirus (HPV) and , that are well established as risk factors for neoplasia. (CT) infections are one of the most common bacterial sexually transmitted infections worldwide, and recent European data confirmed a continuous rise across Europe. The infection is often asymptomatic in both sexes, requiring a screening program for early detection. Notwithstanding, not all countries in Europe have it. can cause chronic and persistent infections, resulting in inflammation, and there are plausible biological mechanisms that link the genital infection with tumorigenesis. Herein, we aimed to understand the epidemiological and biological plausibility of CT genital infections causing endometrial, ovarian, and cervical tumors. Also, we covered some of the best suitable in vitro techniques that could be used to study this potential association. In addition, we defend the point of view of a personalized medicine strategy to treat those patients through the discovery of some biomarkers that could allow it. This review supports the need for the development of further fundamental studies in this area, in order to investigate and establish the role of chlamydial genital infections in oncogenesis.
PubMed: 38930508
DOI: 10.3390/microorganisms12061126 -
Biology May 2024Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to...
Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to long-term physiological consequences. This study was able to identify highly preserved modules and key hub genes that are mainly associated with gynecological diseases, represented by endometriosis (EM), ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), through the weighted gene co-expression network analysis (WGCNA) of microarray datasets sourced from the Gene Expression Omnibus (GEO) database. Five highly preserved modules were observed across the EM (GSE51981), OC (GSE63885), CC (GSE63514), and EC (GSE17025) datasets. The functional annotation and pathway enrichment analysis revealed that the highly preserved modules were heavily involved in several inflammatory pathways that are associated with transcription dysregulation, such as NF-kB signaling, JAK-STAT signaling, MAPK-ERK signaling, and mTOR signaling pathways. Furthermore, the results also include pathways that are relevant in gynecological disease prognosis through viral infections. Mutations in the gene that encodes for ERα, which were shown to also affect signaling pathways involved in inflammation, further indicate its importance in gynecological disease prognosis. Potential drugs were screened through the Drug Repurposing Encyclopedia (DRE) based on the up-and downregulated hub genes, wherein a bacterial ribosomal subunit inhibitor and a benzodiazepine receptor agonist were the top candidates. Other drug candidates include a dihydrofolate reductase inhibitor, glucocorticoid receptor agonists, cholinergic receptor agonists, selective serotonin reuptake inhibitors, sterol demethylase inhibitors, a bacterial antifolate, and serotonin receptor antagonist drugs which have known anti-inflammatory effects, demonstrating that the gene network highlights specific inflammatory pathways as a therapeutic avenue in designing drug candidates for gynecological diseases.
PubMed: 38927277
DOI: 10.3390/biology13060397 -
BMJ Case Reports Jun 2024Malakoplakia is a rare granulomatous, chronic inflammatory disease generally affecting the urogenital organs, though it can arise in other organs. The clinical...
Malakoplakia is a rare granulomatous, chronic inflammatory disease generally affecting the urogenital organs, though it can arise in other organs. The clinical manifestations of malakoplakia vary depending on the affected organ. The final diagnosis is confirmed by the presence of Michaelis-Gutmann bodies on pathology. This report describes a case of pelvic malakoplakia accompanied by an ovarian tumour-cutaneous fistula, initially misdiagnosed as advanced ovarian cancer invading the anterior abdominal wall with left pleural effusion based on imaging studies and increased serum carbohydrate antigen 19-9. The patient underwent left thoracentesis and fluid collection from the fistula tract for cytology, which showed no malignancy. She underwent primary debulking surgery, including removal of the fistula tract from anterior abdominal wall. Histopathological examination revealed malakoplakia coexisting with mucinous cystadenoma of the left ovary. For postoperative management, she received prolonged oral antibiotics for 6 months. There was no evidence of disease recurrence at the 24-month follow-up.
Topics: Humans; Female; Ovarian Neoplasms; Malacoplakia; Diagnosis, Differential; Cutaneous Fistula; Cystadenoma, Mucinous; Middle Aged; Pelvis
PubMed: 38914526
DOI: 10.1136/bcr-2024-260990 -
Gynecology and Minimally Invasive... 2024We aimed to evaluate the surgical results for ectopic pregnancy (EP) treated at Fukushima Red Cross Hospital for over a 20-year period from 2002 to 2021.
OBJECTIVES
We aimed to evaluate the surgical results for ectopic pregnancy (EP) treated at Fukushima Red Cross Hospital for over a 20-year period from 2002 to 2021.
MATERIALS AND METHODS
We evaluated the incidence, surgical procedures, site of implantation, amount of hemoperitoneum, and the proportion of cases with risk factors of EP.
RESULTS
Two hundred and fifty-nine cases of EP were treated surgically. The incidence of EP seemed to be gradually decreasing in recent years. By pregnancy site, 235 (90.7%) of EPs were tubal pregnancies (TPs), 13 in interstitial pregnancies (IPs), 7 in ovarian pregnancies, and 4 in peritoneal pregnancies. For IPs, human chorionic gonadotropin (hCG) levels were statistically higher than with TP and intraperitoneal bleeding was less than with other EP sites. Thirty-nine patients (15.0%) were with massive hemoperitoneum (>500 mL), and laparoscopic surgery was performed in all patients with massive hemoperitoneum except in two patients. The proportion of cases with risk factors for EP such as infection or history of smoking was 5.4% and 40.6%, respectively. Epidemiological research shows that the number of patients with chlamydia infection, rates of smokers, or the occurrence of EP with assisted reproductive technology has been decreasing in recent years in Japan.
CONCLUSION
Appropriate surgical intervention should be selected while considering such as facility capabilities, context, and surgeon skill, especially in critical cases, such as cases involving massive hemoperitoneum and hemorrhagic shock. The recent presumed decrease in the occurrence of EP may partly be associated with the decrease in the occurrence of risk factors.
PubMed: 38911310
DOI: 10.4103/gmit.gmit_53_23 -
Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Female; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Mixed Connective Tissue Disease; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964