A Systematic Review of Semaglutide's Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies.

Since we aim to test new options to find medication for cognitive disorders, we have begun to assess the effect of semaglutide and to conduct a review gathering studies that have attempted this purpose. This systematic review focuses on the cognitive effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), in the context of neurological and cognitive impairment. Semaglutide, a synthetic GLP-1 analog, showcased neuroprotective effects beyond metabolic regulation. It mitigated apoptosis and improved cognitive dysfunction in cerebrovascular disease, suggesting broader implications for neurological well-being. Also, studies highlighted GLP-1 RAs' positive impact on olfactory function in obese individuals with type 2 diabetes, on neurodegenerative disorders, multiple sclerosis, and endotoxemia. In order to analyze current studies that assess the impact of semaglutide on cognitive function, a literature search was conducted up to February 2024 on two online databases, MEDLINE (via PubMed) and Web of Science Core Collection, as well as various websites. Fifteen studies on mice populations and two studies on cell lines were included, analyzed, and assessed with bias-specific tools. The neuroprotective and anti-apoptotic properties of GLP-1 and its analogs were emphasized, with animal models and cell line studies demonstrating enhanced cognitive function. While promising, limitations include fewer studies, highlighting the need for extensive research, particularly in the human population. Even though this medication seems promising, there are significant limitations, one of which is the lack of studies on human subjects. Therefore, this review aims to gather current evidence.

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

Chronic Pelvic Puzzle: Navigating Deep Endometriosis with Renal Complications.

This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of symptoms, including chronic pelvic pain, urinary tract issues, and severe deep adenomyosis. The diagnostic journey was protracted, emphasizing the need for early recognition and intervention in such cases. A thorough evaluation, including laparoscopic examination and histopathological analysis, revealed the extensive presence of endometriotic lesions in various pelvic and renal structures, ultimately leading to left hydronephrosis. The report underscores the significance of timely diagnosis and surgical intervention to prevent irreversible renal damage. This case provides valuable insights into the management of deep endometriosis with renal involvement and the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided.

Histopathological evaluation of cutaneous malignant melanoma: A retrospective study.

Malignant melanoma is a melanocytic neoplasm with a steadily increasing incidence worldwide. In order to define a proper diagnostic protocol and to establish an accurate prognostic method for the disease, specific biomarkers are of notable importance. Their contribution is also significant in the treatment of melanoma for the improvement of newer and more targeted therapeutic approaches. To emphasize the importance of specific immune markers in the diagnosis of melanoma, immunohistochemical analysis was performed on 56 formalin-fixed paraffin-embedded cutaneous melanomas. Besides the traditional prognostic factors, depth of invasion and mitotic rate, the markers tested in the present study were S100 protein family, Melan A, Ki67 and HMB-45. The present results indicated that immunocytochemistry represents a valuable test in the diagnosis and treatment of malignant melanoma and each biomarker had different associations with the progression and prognosis of the disease. Patients with S100 expression were 4.83 times (95% CI=1.2-20.8) more likely to suffer a relapse, whereas patients with a Ki67 expression of >30% had a 5.41-fold higher risk (95% CI=1.3-22.0). The correlation between S100 and the Breslow depth was statistically significant (r-value: 0.43; P=0.027). In addition, the importance of a multidisciplinary team including a plastic surgeon, anatomopathologist and oncologist was highlighted.

Dynamics of serum α-fetoprotein in viral hepatitis C without hepatocellular carcinoma.

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α-fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ-glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV-infected patients, with no reversibility 12 weeks after successful therapy.

Hypocalcemia: A possible risk factor for anastomotic leak in digestive surgery.

Anastomotic leaks (ALs) remain the most severe complication in digestive surgery, as well as the most consumptive in terms of human and financial resources. There is an abundance of international research which has focused on identifying and correcting risk factors, and on individualized surgical management as well. The most frequent risk factors are male sex, obesity, diabetes, advanced malignant disease, ASA score, perioperative blood loss or perioperative transfusion, long operation time, emergency operation and altered nutritional status. The aim of the present study was to measure the preoperative serum calcium level and to find a possible correlation between calcium levels and the risk of AL occurrence. A retrospective analysis of medical records for 122 patients who underwent surgical gut resection with anastomosis for different pathologies was carried out. Preoperative serum calcium level and the occurrence of AL was noted. The results revealed that the average value of total blood calcium was 8.78 mg/dl, without a significant difference in sex groups. Hypocalcemia was identified in 44 patients (36.1%). AL was identified in 8 patients (6.6%), with a statistically insignificant difference between male and female patients. The average value of blood calcium in the AL patient group was 8.07 mg/dl, while in patients without AL the average value was 8.83 mg/dl. Hypocalcemia, defined as a serum calcium level below 8.5 mg/dl, was observed in 7 of the 8 patients presenting with AL (87.5%) and 37 patients who did not present with AL (32.5%), a significant difference with which to consider and include hypocalcemia in the group of risk factors for AL (P=0.001). In conclusion, preoperative low serum calcium level can represent a risk factor for AL in digestive surgery.

Impact of adipose tissue in chronic kidney disease development (Review).

Obesity is a worldwide pandemic health issue. Obesity is associated with the pathogenesis of type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, cancer, and kidney diseases. This systemic disease can affect the kidneys by two mechanisms: Indirectly through diabetes mellitus (DM) and hypertension and directly through adipokines secreted by adipose tissue. Obesity is a risk factor for chronic kidney disease (CKD), which is associated with an increased risk of morbidity and mortality among the adult population. Increased visceral adipose tissue leads to renal glomerular hyperfiltration and hyperperfusion, which may lead to glomerular hypertrophy, proteinuria, and CKD development. Adipokines are hormones produced by fat tissue. They are involved in energy homeostasis, sugar and fat metabolism, reproduction, immunity, and thermogenesis control. Hormones and cytokines secreted by adipose tissue contribute to the development and progression of CKD. Decreased serum or urinary adiponectin levels are specific in diabetic and non-diabetic CKD patients, while leptin presents increased levels, and both are associated with the development of glomerulopathy. Excessive adipose tissue is associated with inflammation, oxidative stress (OS), insulin resistance and activation of the renin angiotensin-aldosterone system (RAAS). Therefore, adipose tissue dysfunction plays an important role in the development of CKD.

PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).

Renal cell carcinoma (RCC) accounts for over 90% of all renal malignancies, and mainly affects the male population. Obesity and smoking are involved in the pathogenesis of several systemic cancers including RCC. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway regulates cell growth, differentiation, migration, survival, angiogenesis, and metabolism. Growth factors, hormones, cytokine and many extracellular cues activate PI3K/AKT/mTOR. Dysregulation of this molecular pathway is frequently reported in human cancers including RCC and is associated with aggressive development and poor survival rate. mTOR is the master regulator of cell metabolism and growth, and is activated in many pathological processes such as tumour formation, insulin resistance and angiogenesis. mTOR inhibitors are used at present as drug therapy for RCC to inhibit cell proliferation, growth, survival, and the cell cycle. Temsirolimus and everolimus are two mTOR inhibitors that are currently used for the treatment of RCC. Drugs targeting the PI3K/AKT/mTOR signalling pathway may be one of the best therapeutic options for RCC.

Kidney aging process and the management of the elderly patient with renal impairment (Review).

As life expectancy increases, a rise in the number of chronically ill patients is observed due to the aging population. Among the various diseases, chronic kidney disease is at present one of the main causes of morbidity and, due to its typical complications, it is also one of the most important causes of mortality in the general population. For these reasons, the understanding of the kidney aging process, its consequences and its adequate management are essential. The judicious use of certain types of drugs, the prevention of episodes of renal injury either by toxic mechanisms or by dehydration are important aspects and are part of the apropriate approach for elderly patients. The most effective treatment of various types of conditions with a negative impact on renal function and for which an increased incidence is known as we age should also be considered. Thus, in the case of elderly patients, in order to protect the kidneys, an integrative approach is recommended, one that includes both elements of prevention and the appropriate treatment of existing diseases.

Management of acute intradialytic cardiovascular complications: Updated overview (Review).

An increasing number of patients require renal replacement therapy through dialysis and renal transplantation. Chronic kidney disease (CKD) affects a large percentage of the world's population and has evolved into a major public health concern. Diabetes mellitus, high blood pressure and a family history of kidney failure are all major risk factors for CKD. Patients in advanced stages of CKD have varying degrees of cardiovascular damage. Comorbidities of these patients, include, on the one hand, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia and, on the other hand, the presence of mineral-bone disorders associated with CKD and chronic inflammation, which contribute to cardiovascular involvement. Acute complications occur quite frequently during dialysis. Among these, the most important are cardiovascular complications, which influence the morbidity and mortality rates of this group of patients. Chronic hemodialysis patients manifest acute cardiovascular complications such as intradialytic hypotension, intradialytic hypertension, arrhythmias, acute coronary syndromes and sudden death. Thus, proper management is extremely important.

Dyselectrolytemia-management and implications in hemodialysis (Review).

Hemodialysis is a method for the renal replacement therapy followed by series of acute and chronic complications. Dyselectrolytemia appears in patients undergoing dialysis through mechanisms related to the chronic kidney disease and/or to the dialysis therapy and for this group of patients it is associated with an increase of morbidity and mortality. The dialysate has a standard composition, which can be modified according to the patient's characteristics. During hemodialysis patients are exposed to 18,000-36.000 litres of water/year, and the water purity along with the biochemical composition of the dialysate are essential. The individualization of the dialysis prescription is recommended for each patient and it has an important role in preventing the occurrence of dyselectrolyemia. The individualization of the treatment prescription according to the blood constants of each patient is the prerogative of the nephrologist and the association of the electrolyte imbalances with the patients cardiovascular mortality explains the importance of paying special attention to them.

Stomach 'tastes' the food and adjusts its emptying: A neurophysiological hypothesis (Review).

The presence of taste receptors and their secondary messengers in stomach raised the possibility that the stomach might play a role in food 'tasting' and consequently, it might initiate specific adaptations of its secretory and motor function. Furthermore, activated taste receptors release a variety of chemical mediators able to modulate the activity of the enteric nervous system (ENS), and also to influence both secretory and motor functions of the stomach. Based on the physiological fundamental structure of a reflex arch, the stimulation of the gastric taste receptors activates sensory neurons of the gastric wall, continues with motor neurons which initiate the contraction of the local smooth muscle fibers. Beyond this, compounds which act on different taste receptors initiate different responses, stimulatory or inhibitory. These interactions may be translated in the gastric ability to selectively evacuate different nutritive compounds into the duodenum. Consequently, sugars could be favored to the detriment of other compounds.

Primary thyroid angiosarcoma in a non-endemic region - a rare case.

Thyroid angiosarcoma (AS) is a specific type of vascular tumor that arises from the endothelial cells, being highly aggressive, with increased recurrence rates and metastasis. It is characterized by positive endothelial markers and co-positive markers for cytokeratins and epithelial membrane antigen. We are describing the case of a 76-year-old patient who presented to the hospital for dyspnea and asthenia. The clinical and paraclinical investigations confirmed the presence of a right large thyroid nodule, which turned out positive at immunostaining for AS. Even if thyroid AS is a rare type of tumor, mainly described in the Alps, one has to take into account that it can evolve in any other regions and should be considered as a differential diagnosis.

Quality of Life in Patients with Surgically Removed Skin Tumors.

Background and Objectives: Skin cancer is one of the most frequently diagnosed malignancies. The main goal of the therapeutic management is total excision with the prevention of recurrence and metastasis. The quality of life of the patients with skin cancer is affected by the morbidity risk, surgery, and cosmetic or functional aspects. The aim of this study was to evaluate the quality of life of patients with skin cancer prior to and post surgical intervention. Material and methods: We performed a prospective study on 247 patients with skin tumors. Quality of life was evaluated through an initial questionnaire that was given to all consenting patients. This was used to determine patients' mobility, selfcare, normal activities, pain, and despair, using a five-point Likert scale. The general autoperceived health state was also recorded using a 100-point scale. The study included the responses of all patients at hospital admission, after one month of surgery, and after one year of surgery. Results: In patients with squamous cell carcinoma (SCC), the general health state indicator statistically significantly decreased one month after surgery and increased at one-year follow-up. In malignant melanoma (MM) patients, mobility, selfcare, normal activities, and discomfort presented a decrease in values one year after surgery, compared to the values registered at hospital admission. In patients with basal cell carcinoma (BCC), all indicators of quality of life presented an impaired value one year after surgery, after a decreasing trend. The general health state indicator statistically significantly increased one month after surgery and after one year. Conclusions: Surgery is one of the main steps in treating skin cancer. It has a great impact on patients' quality of life because of pain andthe effect on mobility and normal activities. Skin cancers influence the quality of life of patients both psychologicallyand physically.