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Gynecological Endocrinology : the... Oct 2023Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and...
BACKGROUND
Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and obesity-associated protein (FTO), a m6A demethylase, is abnormal in the occurrence of ovarian diseases. However, the mechanism of FTO in the pathogenesis of PCOS is still unclear.
METHODS
The level of FTO in clinical samples, PCOS rat with hyperandrogenism and granulosa cells (GCs) lines effected by DHT were investigated by ELISA, qRT-PCR, WB, and IHC, while m6A RNA methylation level was studied by m6A Colorimetric and androgen level was tested through ELISA. Changes in steroid hormone synthetase and androgen receptor (AR)/prostate-specific antigen (PSA) levels were visualized by WB after transient transfection silenced FTO. The effect of DHT combined with FTO inhibitor meclofenamic acid (MA) on FTO, AR/PSA, and AKT phosphorylation were also demonstrated by WB. The co-localization of FTO and AR in KGN cells was analyzed by confocal microscopy, and the physiological interaction between FTO and AR was studied by Co-IP assay. The effect of FTO-specific inhibitor MA, AKT phosphorylation inhibitor LY294002, and the combined them on GCs proliferation and cell cycle were evaluated by drug combination index, EDU assay, and flow cytometry analysis.
RESULTS
FTO expression was upregulated in follicular fluid and GCs in PCOS patients clinically. The high FTO expression in patients was negative with the level of m6A, but positive with the level of androgen. The upregulation of FTO was accompanied with a decrease in the level of m6A in PCOS rat with hyperandrogenism. Dihydrotestosterone (DHT) promoted the FTO expression and inhibited m6A content as a dose-dependent way . In contrast, suppression of FTO with siRNA attenuated the expression of steroid hormone synthetase such as CYP11A1, CYP17A1, HSD11B1, HSD3B2 except CYP19A1 synthetase, ultimately inducing the decrease of androgen level. Suppression of FTO also decreased the biological activity of androgen through downregulation AR/PSA. MA treatment as the specific FTO antagonist decreased cell survival in time- and dose-dependent way in GCs lines. Correspondingly, MA treatment decreased the expression of FTO, AR/PSA expression, and AKT phosphorylation in the presence of DHT stimulation. Additionally, we also speculate there is a potential relation between FTO and AR according to FTO was co-localized and interacted with AR in KGN cells. Compared with AKT phosphorylation inhibitor LY294002 or MA alone, LY294002 combined with MA synergistically inhibited cell survival and increased G2/M phase arrest in GC line.
CONCLUSIONS
We first evaluated the correlation of FTO and m6A in PCOS clinically, and further explored the mechanism between FTO and hyperandrogenism in PCOS animal and cell models. These findings contributed the potential therapy by targeting the FTO for hyperandrogenism in PCOS.
Topics: Animals; Female; Humans; Rats; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Androgens; Dihydrotestosterone; Granulosa Cells; Hyperandrogenism; Ligases; Polycystic Ovary Syndrome; Prostate-Specific Antigen; Proto-Oncogene Proteins c-akt
PubMed: 37931646
DOI: 10.1080/09513590.2023.2276167 -
BMC Cancer Mar 2024Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles... (Review)
Review
Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.
Topics: Male; Humans; Adenocarcinoma; Pancreatic Neoplasms; Extracellular Vesicles; Exosomes; MicroRNAs; Biomarkers; DNA; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 38454346
DOI: 10.1186/s12885-024-11819-4 -
Annals of Medicine and Surgery (2012) Apr 2024Guillain-Barre syndrome (GBS) has been found to have some interesting association with vaccinations. This paper mainly focuses on exploring different associations... (Review)
Review
BACKGROUND AND OBJECTIVE
Guillain-Barre syndrome (GBS) has been found to have some interesting association with vaccinations. This paper mainly focuses on exploring different associations between COVID-19 vaccination and GBS.
METHODS
Electronic databases such as PubMed, Google Scholar, Cochrane, and Embase were searched using MESH terms for case reports published till 1 August 2023 from which 70 case reports were documented involving 103 individuals from 23 different countries.
RESULT AND DISCUSSION
The case reports were from a wide range of individuals aged from 13 to 87 years with an average age of 53±20 interquartile range years along with male predominance. The average time between receiving the vaccine and the onset of symptoms was 13.08±2.14 days. Prominent clinical features included back pain, facial diplegia, weakness, and paraesthesia whereas the main diagnostic studies were cerebrospinal fluid (CSF) analysis and electromagnetic studies. The principal diagnostic clue was albumin-cytological dissociation in CSF while being negative for anti-ganglioside antibodies or SARS-CoV-2. Available treatment options consisted of intravenous immunoglobulin and Plasmapheresis. Patients with comorbidities such as diabetes mellitus, hypertension, dyslipidemia, permanent atrial fibrillation, hypothyroidism, Hashimoto's thyroiditis, Chronic Obstructive Pulmonary Disease, asthma, osteoporosis, migraine, rheumatoid arthritis, osteoarthritis, ulcerative colitis, coeliac disease, seizures, bipolar disorder, endometriosis, multiple sclerosis, bell's palsy, squamous cell carcinoma, prostate cancer were included in our study.
CONCLUSION
Overall, this review evaluated innovative and clinically relevant associations between COVID-19 vaccination and GBS. Understanding of this uncommon potential side effect of COVID-19 vaccination is crucial for prompt diagnosis and appropriate treatment. Importantly, GBS should not be considered a contraindication to vaccination. This underscores the importance of ongoing research to enhance the safety and efficacy of COVID-19 vaccination efforts.
PubMed: 38576928
DOI: 10.1097/MS9.0000000000001915 -
P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.Military Medical Research May 2024Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific...
BACKGROUND
Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.
METHODS
The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.
RESULTS
P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.
CONCLUSION
P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.
Topics: Male; Prostatic Hyperplasia; Porphyromonas gingivalis; Rats; Humans; Animals; Interleukin-6; Receptors, Interleukin-6; Prostate; Periodontitis; Aged; Middle Aged; Rats, Sprague-Dawley; Disease Models, Animal; Signal Transduction
PubMed: 38764065
DOI: 10.1186/s40779-024-00533-8 -
JCI Insight Dec 2023Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and...
Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and skin. Patients develop progressive edema of the affected extremity due to retention of protein-rich lymphatic fluid. Despite compression therapy, patients progress to chronic lymphedema in which noncompressible fibrosis and adipose tissue are deposited within the extremity. The presence of fibrosis led to our hypothesis that rosiglitazone, a PPARγ agonist that inhibits fibrosis, would reduce fibrosis in a mouse model of secondary lymphedema after hind limb lymphadenectomy. In vivo, rosiglitazone reduced fibrosis in the hind limb after lymphadenectomy. Our findings verified that rosiglitazone reestablished the adipogenic features of TGF-β1-treated mesenchymal cells in vitro. Despite this, rosiglitazone led to a reduction in adipose tissue deposition. Single-cell RNA-Seq data obtained from human tissues and flow cytometric and histological evaluation of mouse tissues demonstrated increased presence of PDGFRα+ cells in lymphedema; human tissue analysis verified these cells have the capacity for adipogenic and fibrogenic differentiation. Upon treatment with rosiglitazone, we noted a reduction in the overall quantity of PDGFRα+ cells and LipidTOX+ cells. Our findings provide a framework for treating secondary lymphedema as a condition of fibrosis and adipose tissue deposition, both of which, paradoxically, can be prevented with a pro-adipogenic agent.
Topics: Male; Female; Humans; Mice; Animals; Receptor, Platelet-Derived Growth Factor alpha; PPAR gamma; Rosiglitazone; Lymphedema; Fibrosis
PubMed: 38131378
DOI: 10.1172/jci.insight.165324 -
ACS Applied Materials & Interfaces Jun 2023Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid...
Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotropic magnetic core-shell-shell nanoparticles (i.e., trimagnetic nanoparticles - TMNPs) with significant magnetothermal conversion following an exchange coupling effect to an external alternating magnetic field (AMF). The functional properties of the best candidate in terms of heating efficiency (i.e., FeO@MnZnFeO@CoFeO) were exploited following surface decoration with PCa cell membranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstrated that the combination of biomimetic dual CM-CPP targeting and AMF responsiveness significantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore, a downregulation of the cell cycle progression markers and a decrease of the migration rate in surviving cells were observed in response to the TMNP-assisted magnetic hyperthermia, suggesting a reduction in cancer cell aggressiveness.
Topics: Male; Humans; Cell-Penetrating Peptides; Hyperthermia, Induced; Nanoparticles; Cell Membrane; Magnetic Fields; Prostatic Neoplasms; Magnetite Nanoparticles
PubMed: 37312240
DOI: 10.1021/acsami.3c07248 -
Cancer Journal (Sudbury, Mass.)The advent of high-throughput technologies has enabled the analysis of minute amounts of tumor-derived material purified from body fluids, termed "liquid biopsies."... (Review)
Review
The advent of high-throughput technologies has enabled the analysis of minute amounts of tumor-derived material purified from body fluids, termed "liquid biopsies." Prostate cancer (PCa) management, like in many other cancer types, has benefited from liquid biopsies at several stages of the disease. Although initially describing circulating tumor cells in blood, the term "liquid biopsy" has come to more prominently include cell-free, circulating tumor DNA, as well as RNA, proteins, and other molecules. They provide tumor molecular information representing the entire, often-heterogeneous disease, relatively noninvasively and longitudinally. Blood has been the main liquid biopsy specimen in PCa, and urine has also proven beneficial. Technological advances have allowed clinical implementation of some liquid biopsies in PCa, in disease monitoring and precision oncology. This narrative review introduces the main types of blood-based PCa liquid biopsies focusing on advances in the past 5 years. Clinical adoption of liquid biopsies to detect and monitor the evolving PCa tumor biology promises to deepen our understanding of the disease and improve patient outcomes.
Topics: Male; Humans; Precision Medicine; Prostatic Neoplasms; Liquid Biopsy; Biopsy; RNA; Biomarkers, Tumor; Neoplastic Cells, Circulating
PubMed: 37471612
DOI: 10.1097/PPO.0000000000000672 -
Urology Case Reports Sep 2023A 25 year old male presented with several weeks of fevers and testicular pain. Workup demonstrated scrotal and prostatic abscesses. Fluid from these following surgical...
A 25 year old male presented with several weeks of fevers and testicular pain. Workup demonstrated scrotal and prostatic abscesses. Fluid from these following surgical drainage revealed Blastomyces dermatitidis. He was treated with 12 months of oral anti-fungal therapy and repeat Blastomyces urine antigen was negative at follow up. While disseminated blastomycosis most commonly presents with pulmonary and cutaneous manifestations, genitourinary symptoms are rarely seen, but important to consider.
PubMed: 37455778
DOI: 10.1016/j.eucr.2023.102489 -
Cancers Aug 2023Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of... (Review)
Review
Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of prostate cancer, as well as its establishment and proliferation, including the necessary steps for metastasis. Here we compiled, for the first time, the important roles of miRNAs in the development, diagnosis, and treatment of bone metastasis, focusing on recent in vivo and in vitro studies. PCa exosomes are proven to promote metastasis-related events, such as osteoblast and osteoclast differentiation and proliferation. Aberrant miRNA expression in PCa may induce abnormal bone remodeling and support tumor development. Furthermore, miRNAs are capable of binding to multiple mRNA targets, a dynamic property that can be harnessed for the development of treatment tools, such as antagomiRs and miRNA mimics, which have emerged as promising candidates in PCa treatment. Finally, miRNAs may serve as noninvasive biomarkers, as they can be detected in tissue and bodily fluids, are highly stable, and show differential expression between nonmetastatic PCa and bone metastatic samples. Taken together, the findings underscore the importance of miRNA expression profiles and miRNA-based tools as rational technologies to increase the quality of life and longevity of patients.
PubMed: 37627055
DOI: 10.3390/cancers15164027 -
Frontiers in Oncology 2023Liquid biopsy as a non-invasive method has a bright future in cancer diagnosis. Tumor-related extracellular vesicles (EVs) and their components (nucleic acids, proteins,... (Review)
Review
Liquid biopsy as a non-invasive method has a bright future in cancer diagnosis. Tumor-related extracellular vesicles (EVs) and their components (nucleic acids, proteins, and lipids) in biofluids may exert multiple functions in tumor growth, metastasis, immune escape, and angiogenesis. Among all the components, nucleic acids have attracted the most interest due to their simplicity of extraction and detection. In this review, the biological functions of EVs in prostate cancer (PCa) genesis and progression were summarized. Moreover, the diagnostic value of EV RNA markers found in clinical body fluid samples was reviewed, including their trends, challenging isolation methods, and diagnostic efficacy. Lastly, because relatively much progress has been made in PCa, studies on EV DNA markers are also discussed.
PubMed: 37456240
DOI: 10.3389/fonc.2023.1201554