Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled growth and spread of abnormal cells. While cancer can be challenging and life-altering, advances in research ...and development have led to the identification of new promising anti-cancer targets. Telomerase is one such target that is overexpressed in almost all cancer cells and plays a critical role in maintaining telomere length, which is essential for cell proliferation and survival. Inhibiting telomerase activity can lead to telomere shortening and eventual cell death, thus presenting itself as a potential target for cancer therapy. Naturally occurring flavonoids are a class of compounds that have already been shown to possess different biological properties, including the anti-cancer property. They are present in various everyday food sources and richly present in fruits, nuts, soybeans, vegetables, tea, wine, and berries, to name a few. Thus, these flavonoids could inhibit or deactivate telomerase expression in cancer cells by different mechanisms, which include inhibiting the expression of hTERT, mRNA, protein, and nuclear translocation, inhibiting the binding of transcription factors to hTERT promoters, and even telomere shortening. Numerous cell line studies and in vivo experiments have supported this hypothesis, and this development could serve as a vital and innovative therapeutic option for cancer. In this light, we aim to elucidate the role of telomerase as a potential anti-cancer target. Subsequently, we have illustrated that how commonly found natural flavonoids demonstrate their anti-cancer activity via telomerase inactivation in different cancer types, thus proving the potential of these naturally occurring flavonoids as useful therapeutic agents.
Dapagliflozin (Farxiga), is an SGLT-2 inhibitor commonly indicated for the treatment of diabetes mellitus type 2 (DM 2), heart failure, and chronic kidney disease. One rare side effect associated ...with SGLT-2 inhibitors is bacterial infection of the genitalia. There are several case reports highlighting the incidence of Fournier's gangrene (FG) in patients who take medications within this drug class. We report a case of FG in a diabetic patient on dapagliflozin who presented following scrotal hydrocelectomy for a large-volume hydrocele. The patient was urgently taken to the operating room for scrotal debridement and recovered well in the post-operative period.
Semen analysis is a basic test for evaluating male fertility potential, as it plays an essential role in driving the future management and treatment of infertility in couples. Manual semen analysis ...includes the evaluation of both macroscopic and microscopic parameters, whereas automated semen analysis is conducted through a computer-aided sperm analysis system and can include additional parameters that are not evaluated by manual analysis. Both quality control (QC) and quality assurance (QA) are important to ensure reproducible results for semen analysis, and represent fundamental checks and balances of all stages (pre-analytical, analytical, and post-analytical) of semen analysis. To ensure accuracy and precision, the laboratory technicians' performance should be evaluated biannually. This narrative review aims to describe standardized laboratory procedures for an accurate assessment of semen parameters that incorporate both QC and QA practices.
Background
Huntington’s disease is one of the rare neurodegenerative diseases caused because of genetic mutation of the Huntingtin gene. The major hallmarks of the condition include motor impairment, ...cognitive decline, and psychiatric symptoms. With no cure and only symptomatic treatments available, early detection and personalized therapy are warranted for managing the disease effectively. Artificial Intelligence has emerged as a transformational tool in healthcare, revolutionizing many parts of medical practice and research, thus holding the potential in detecting, monitoring, and managing Huntington’s disease.
Main body of abstract
Artificial Intelligence’s role in Huntington’s disease includes a variety of applications like medical image analysis and predictive analytics. AI-driven algorithms are utilized to analyze brain imaging data in medical image analysis. Deep learning and convolutional neural networks (CNNs) aid in the detection of subtle brain changes and the identification of illness biomarkers, allowing for the early diagnosis of the disease. Additionally, the predictive analytics capabilities of AI are used to analyze disease development and forecast clinical outcomes. AI models can identify illness patterns, estimate the rate of functional decline, and assist doctors in making educated decisions about treatment methods and care planning by analyzing patient data.
Conclusions
With clinical practice and research integrated with Artificial Intelligence technologies, we can significantly improve the quality of life of individuals affected with Huntington’s disease. This integration holds the potential to develop effective personalized interventions. Nevertheless, collaborative efforts among doctors, researchers, and technology sound developers would be key to the successful implementation of AI in HD.
Graphical Abstract
Metastasis to the penis is an extremely rare entity. Malignant priapism is defined as a persistent, nonsexual erection that is refractory to pharmacologic treatment, corporal aspiration, and surgical ...shunts. Furthermore, it is typically a hallmark of an advanced cancer that has metastasized, most commonly from regional organs like the prostate or bladder. We report an unusual case of malignant priapism in the setting of metastatic follicular thyroid carcinoma. To date, this is the second reported case of penile metastasis due to thyroid carcinoma and the first incidence of priapism secondary to follicular thyroid carcinoma metastasis.
Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as ...the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines.
Antioxidant supplementation in idiopathic male infertility has a beneficial effect on semen parameters. However, the molecular mechanism behind this effect has not been reported. The objective of ...this study was to evaluate the sperm proteome of idiopathic infertile men pre- and post-antioxidant supplementation. Idiopathic infertile men were provided with oral antioxidant supplementation once daily for a period of 6 months. Of the 379 differentially expressed proteins (DEPs) between pre- and post-antioxidant treatment patients, the majority of the proteins (
= 274) were overexpressed following antioxidant treatment. Bioinformatic analysis revealed the activation of oxidative phosphorylation pathway and upregulation of key proteins involved in spermatogenesis, sperm maturation, binding of sperm, fertilization and normal reproductive function. In addition, the transcriptional factors associated with antioxidant defense system (PPARGC1A) and free radical scavenging (NFE2L2) were predicted to be functionally activated post-treatment. Key DEPs, namely, NDUFS1, CCT3, PRKARA1 and SPA17 validated by Western blot showed significant overexpression post-treatment. Our novel proteomic findings suggest that antioxidant supplementation in idiopathic infertile men improves sperm function at the molecular level by modulating proteins involved in CREM signaling, mitochondrial function and protein oxidation. Further, activation of TRiC complex helped in nuclear compaction, maintenance of telomere length, flagella function, and expression of zona pellucida receptors for sperm-oocyte interaction.
The advent of intracytoplasmic sperm injection (ICSI) has changed the human reproduction landscape by overcoming several limitations related to both male and female infertility factors. However, ...despite the development of new technologies, the live-birth rate with ICSI has not exceeded 30%. In order to improve assisted reproductive technology outcomes, advanced sperm function analysis have gained increased attention and the effects of sperm DNA fragmentation (SDF) on assisted reproduction success are being extensively studied. Utilizing ejaculated sperm with an elevated SDF has been found to result in poor ICSI outcomes. Furthermore, studies have reported that testicular sperm has lower SDF level, when compared to ejaculated sperm. This has led a number of clinicians world-wide to offer testicular sperm retrieval for ICSI in non-azoospermic males with high SDF. This practice has remained controversial due to lack of high quality evidence.
The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×10
/mL of semen. Granular leukocytes when ...activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including
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can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.
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