Dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC. AIM OF THE STUDY: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC. MATERIALS AND METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (" dermoscopy" OR " dermatoscopy" OR " videodermoscopy" OR " videodermatoscopy" OR " reflectance confocal microscopy") AND " Merkel cell carcinoma". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account. RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells. CONCLUSION: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200 mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21st day of the treatment with 500 mg/kg ethanolic extract.

Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research.

Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.

New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Awake craniotomies in South America: Advancements, challenges, and future prospects.

BACKGROUND: Awake craniotomy has emerged as an advanced surgical technique, characterized by keeping the patient awake during brain surgery. In South America, awake craniotomies have grained traction in neurosurgical practices across various medical centres and hospitals, with notable practitioners contributing to its growth and refinement in the region. PURPOSE: This study aims to explore the integration and impact of awake craniotomies in South American neurosurgical practices. The focus is on understanding the benefits, challenges, and potential transformative effects of the procedure in the region. RESEARCH DESIGN: A comprehensive narrative review and analysis through a thorough examination of the existing literature. RESULTS: The findings indicate that awake craniotomies in South America offer substantial benefits, including cost savings thorugh reduced hospitalization time, quicker recovery and decreased morbidity. Enhanced safety, effective pain management and reduced anaesthesia also contribute to this. CONCLUSION: Whilst the adaptation of awake craniotomies in South America holds great promise in transforming neurosurgical care in the region, significant challenges hinder its widespread adoption. Inadequate infrastructure, limited access to equipment, financial instability, and shortages in trained healthcare providers represent challenges that need to be addressed.

Therapeutic Potential of Cornus Genus: Navigating Phytochemistry, Pharmacology, Clinical Studies, and Advanced Delivery Approaches.

The genus Cornus (Cornaceae) plants are widely distributed in Europe, southwest Asia, North America, and the mountains of Central America, South America, and East Africa. Cornus plants exhibit antimicrobial, antioxidative, antiproliferative, cytotoxic, antidiabetic, anti-inflammatory, neuroprotective and immunomodulatory activities. These plants are exploited to possess various phytoconstituents such as triterpenoids, iridoids, anthocyanins, tannins and flavonoids. Pharmacological research and clinical investigations on various Cornus species have advanced significantly in recent years. Over the past few decades, a significant amount of focus has also been made into developing new delivery systems for Cornus mas and Cornus officinalis. This review focuses on the morphological traits, ethnopharmacology, phytochemistry, pharmacological activities and clinical studies on extracts and active constituents from plants of Cornus genus. The review also highlights recent novel delivery systems for Cornus mas and Cornus officinalis extracts to promote sustained and targeted delivery in diverse disorders. The overwhelming body of research supports the idea that plants from the genus Cornus have therapeutic potential and can be investigated in the future for treatingseveral ailments.

The therapeutic value of Myrtus communis L.: an updated review.

Myrtus communis L. (Family: Myrtaceae) is naturally found in the western part of Asia, Southern Europe, and North Africa. It has been reportedly applied in pharmaceutical industry, traditional medicine, cosmetics, spices, and food. Pubmed, Google scholar, Web of Science, and Scopus were utilized to seek out relevant content concerning the therapeutic potential of M. communis. Subsequently, we conducted a review to identity noteworthy updates pertaining to M. communis. Myrtle berries, leaves, seeds, and essential oils are natural sources of several nutrients and bioactive compounds with marked health effects. The chemical analysis showed that M. communis contained oils, alkaloids, flavonoids, phenolics, coumarins, saponosides, tannins, quinines, and anthraquinones. A pharmacological investigation revealed that M. communis possessed anti-inflammatory, analgesic, antimicrobial, antiparasitic, antioxidant, antidiabetic, anticancer, antimutagenic, immunomodulatory, dermatological, cardiovascular, central nervous system, and gastrointestinal protective effects, among numerous other biological effects. This current review focused on the biochemical, pharmacological, therapeutic effects, and various biological activities of different parts of M. communis. It signifies that M. communis is a therapeutic plant with numerous applications in medicine and could be used as a drug isolate based on its safety and effectiveness.

The role of Aquaporins in tumorigenesis: implications for therapeutic development.

Aquaporins (AQPs) are ubiquitous channel proteins that play a critical role in the homeostasis of the cellular environment by allowing the transit of water, chemicals, and ions. They can be found in many different types of cells and organs, including the lungs, eyes, brain, glands, and blood vessels. By controlling the osmotic water flux in processes like cell growth, energy metabolism, migration, adhesion, and proliferation, AQPs are capable of exerting their regulatory influence over a wide range of cellular processes. Tumour cells of varying sources express AQPs significantly, especially in malignant tumours with a high propensity for metastasis. New insights into the roles of AQPs in cell migration and proliferation reinforce the notion that AQPs are crucial players in tumour biology. AQPs have recently been shown to be a powerful tool in the fight against pathogenic antibodies and metastatic cell migration, despite the fact that the molecular processes of aquaporins in pathology are not entirely established. In this review, we shall discuss the several ways in which AQPs are expressed in the body, the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma.

The Use of Isoflavones as Lung Cancer Chemoprevention Agents and their Implications in Treatment through Radio Sensitization.

Epidemiological trends in cancer research show that lung cancer can affect up to 1 in 15 men and 1 in 17 women. With incidence rates as high as these and significant associated mortality and morbidity, it is no wonder that lung cancer is one of the main areas of research focused on cancer. Advances in targeted treatments and specialized irradiation protocols have allowed the treatment of more advanced cases. However, as the patient numbers grow, so does the need for cancer-preventive strategies. The present narrative review focuses on soy isoflavones' role in the chemoprevention of lung cancer and their possible role in therapeutic adjuncts. Laboratory studies on lung cancer cell lines have shown that isoflavones can induce apoptosis, tamper with the expression of proliferative molecular pathways, and even reduce tumor angiogenesis. Additionally, population-level studies have emerged that correlate the consumption of isoflavonoids with reduced risk for the development of lung cancer. Interestingly enough, the literature also contains small-scale studies with evidence of isoflavones being effective chemotherapeutic adjuncts that are currently understudied. Our literature review underlines such findings and provides a call for the enhancement of research regarding naturally occurring dietary products with possible anticarcinogenic effects.

Current trends and challenges: The landscape of perioperative mortality in intracranial surgeries in low- and middle-income settings: A narrative review.

Background and Aims: Intracranial surgeries are pivotal in treating cerebral pathologies, particularly in resource-limited contexts, utilizing techniques such as craniotomy, transsphenoidal approaches, and endoscopy. However, challenges in low and middle income countries (LMICs), including resource scarcity, diagnostic delays, and a lack of skilled neurosurgeons, lead to elevated perioperative mortality (POM). This review seeks to identify major contributors to these challenges and recommend solutions for improved patient outcomes in neurosurgical care within LMICs. Methods: This review examines POM in LMICs using a detailed literature search, focusing on studies from these regions. Databases like PubMed, EMBASE, and Google Scholar were utilized using specific terms related to "intracranial surgery," "perioperative mortality," "traumatic brain injuries," and "LMICs." Inclusion criteria covered various study designs and both pediatric and adult populations while excluding stand-alone abstracts and case reports. Results: POM rates for intracranial surgeries differ widely across many low and middle-income regions: Africa sees rates from 2.5% to 39.1%, Asia between 3.6% and 34.8%, and Latin America and the Caribbean have figures ranging from 1.3% to 12%. The POM rates in LMICs were relatively higher compared to most first-world countries. The high POM rates in LMICs can be attributed to considerable delays and compromises in neurosurgical care delivery, exacerbated by late diagnoses and presentations of neurosurgical pathologies. This, coupled with limited resources, underdeveloped infrastructure, and training gaps, complicates intracranial disease management, leading to elevated POM. Conclusion: Intracranial POM is a pronounced disparity within the neurosurgical field in LMICs. To mitigate intracranial POM, it is imperative to bolster healthcare infrastructure, amplify personnel training, foster global partnerships, and harness technologies like telemedicine. Tackling socioeconomic obstacles and prioritizing early detection through sustained funding and policy shifts can substantially enhance patient outcomes.

Color Analysis of Merkel Cell Carcinoma: A Comparative Study with Cherry Angiomas, Hemangiomas, Basal Cell Carcinomas, and Squamous Cell Carcinomas.

Merkel cell carcinoma (MCC) is recognized as one of the most malignant skin tumors. Its rarity might explain the limited exploration of digital color studies in this area. The objective of this study was to delineate color alterations in MCCs compared to benign lesions resembling MCC, such as cherry angiomas and hemangiomas, along with other non-melanoma skin cancer lesions like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), utilizing computer-aided digital color analysis. This was a retrospective study where clinical images of the color of the lesion and adjacent normal skin from 11 patients with primary MCC, 11 patients with cherry angiomas, 12 patients with hemangiomas, and 12 patients with BCC/SCC (totaling 46 patients) were analyzed using the RGB (red, green, and blue) and the CIE Lab color system. The Lab color system aided in estimating the Individual Typology Angle (ITA) change in the skin, and these results are documented in this study. It was demonstrated that the estimation of color components can assist in the differential diagnosis of these types of lesions because there were significant differences in color parameters between MCC and other categories of skin lesions such as hemangiomas, common skin carcinomas, and cherry hemangiomas. Significant differences in values were observed in the blue color of RGB (p = 0.003) and the b* parameter of Lab color (p < 0.0001) of MCC versus cherry angiomas. Similarly, the mean a* value of Merkel cell carcinoma (MCC) compared to basal cell carcinoma and squamous cell carcinoma showed a statistically significant difference (p < 0.0001). Larger prospective studies are warranted to further validate the clinical application of these findings.

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aß). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aß. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aß and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aß. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aß clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

The possible role furin and furin inhibitors in endometrial adenocarcinoma: A narrative review.

BACKGROUND: Endometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC. RECENT FINDINGS: Furin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro-metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro-renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation. CONCLUSION: Furin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro-renin receptor, CD109, and TGF-ß. As well, EAC-mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.

Therapeutic potential of Lawsonia inermis Linn: a comprehensive overview.

Lawsonia inermis Linn, commonly known as henna, is a member of the Lythraceae family and has been found to contain a variety of compounds with both industrial and medicinal applications in its stem, bark, roots, flowers, and seeds. This report provides a comprehensive review of the bioactive components, pharmacological activities, pharmacokinetics, and pharmacological side effects of Lawsonia inermis. Relevant materials were gathered from Google Scholar, PubMed, Scopus, and Web of Science and reviewed for important properties and updates about the plant. Lawsonia inermis contains a variety of bioactive compounds, including flavonoids, coumarins, triterpenoids, steroids, xanthones, polyphenols, fatty acids, alkaloids, quinones, tannins, leucocyandin, epicatechin, catechin, and quercetin. The plant is been traditionally used to treat numerous conditions, including ulcers, bronchitis, lumbago, hemicrania, leukoderma, scabies, boils, ophthalmic disorders, hair loss, and jaundice. It has also been found to possess a range of pharmacological activities, including antioxidant, anti-inflammatory, analgesic, antiparasitic, hepatoprotective, antifungal, antitumor, wound healing, and hypoglycemic effects. The potential of Lawsonia inermis for various biological applications is promising, and further studies are needed to fully explore its therapeutic benefits for various diseases of public health. Concern advances in drug development could enable the characterization of various bioactive constituents and facilitate their development and application for the benefit of humanity.