Pyrimidine-triazole-tethered tert-butyl-piperazine-carboxylate suppresses breast cancer by targeting estrogen receptor signaling and ß-catenin activation.

Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/ß-catenin pathway.

Zinc pathogenic importance in correcting immunity and restoring public health in the post-COVID period: An overview.

CONTEXT: The problem of correcting immune system function and compensating for co-morbidities becomes particularly clinically significant in the post-COVID period. There is evidence that certain trace elements in the human body, particularly zinc ions, play a critical role in restoring the function of the immune system and internal organs. OBJECTIVE: To analyze the mechanisms of zinc action maintaining the body homeostasis in order to justify pathogenetically the inclusion of zinc drugs in the therapy of patients in the post-COVID period. METHODS: Data from Elsevier, Global Health, PubMed-NCBI, Embase, MEDLINE, Scopus, Research gate, RSCI Scopus, Cochrane Library, Google Academy, e-LIBRARY.RU and CyberLeninka were used. RESULTS: This review showed that the importance of zinc in maintaining body homeostasis in the post-COVID period is determined by its multifaceted effect on all parts of the immune system, its anti-inflammatory activity, antimicrobial properties and participation in the restoration of internal organ function. Elimination of zinc deficiency in the post-COVID period is essential to support immunity, compensate for comorbidities and reduce the risk of complications. The impossibility of synthesizing zinc in the body requires its constant intake in sufficient quantities. Zinc levels are significantly reduced after infectious diseases, as this element is specifically distributed to organs and tissues to maintain immunological and metabolic functions. The degree of zinc deficiency is associated with the severity of COVID-19 and the post-COVID period. It is pathogenetically justified to prescribe zinc drugs in the post-COVID period, the choice of which should take into account comorbidities and severity of hypozincemia. CONCLUSION: Regularly administered therapy with zinc drugs in the post-COVID period will help correct the population immunity and restore public health.

Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

Paneth cells: Maintaining dynamic microbiome-host homeostasis, protecting against inflammation and cancer.

The human intestines are constantly under the influence of numerous pathological factors: enteropathogenic microorganisms, food antigens, physico-chemical stress associated with digestion and bacterial metabolism, therefore it must be provided with a system of protection against adverse impact. Recent studies have shown that Paneth cells play a crucial role in maintaining homeostasis of the small intestines. Paneth cells perform many vital functions aimed at maintaining a homeostatic balance between normal microbiota, infectious pathogens and the human body, regulate the qualitative composition and number of intestinal microorganisms, prevent the introduction of potentially pathogenic species, and protect stem cells from damage. Paneth cells take part in adaptive and protective-inflammatory reactions. Paneth cells maintain dynamic balance between microbial populations, and the macroorganism, preventing the development of intestinal infections and cancer. They play a crucial role in gastrointestinal homeostasis and may be key factors in the etiopathological progression of intestinal diseases.

Vaccination as a Significant Factor Influencing the Psychoemotional State of Medical Students During the Sars-Cov-2 Pandemic: An International Aspect.

Background: The rapid spread of SARS-COV-2, characterized by its severe course in the absence of effective specific treatment for this infection, may become a significant risk factor for psycho-emotional disorders' emergence during this pandemic. One of the vulnerable groups in the current situation are first-year medical students, whose problems associated with an unfavorable sanitary-epidemiological situation and an increased infection risk are compounded by the difficulties of adapting to specific professional environments. In this situation, along with strict adherence to nonspecific prevention methods, the mass student SARS-COV-2 vaccination acquires particular importance. Objective: To compare the attitudes of first-year medical students in Russia and Azerbaijan toward SARS-COV-2 immunization and to assess the vaccination impact on the student's psycho-emotional state during the SARS-COV-2 pandemic. Materials and Methods: The study involved 594 first-year students at the Moscow and Baku branches of Sechenov University. The Google Forms platform was used to conduct an anonymous sociological survey. To compare the psychoemotional state of vaccinated freshmen and non-vaccinated students, we used the State-Trait Anxiety Inventory, STAI, to assess reactive anxiety and the Beck Depression Inventory test - to diagnose depressive symptoms. The online survey was conducted during the fourth wave of coronavirus infection. WHO official sources were used to analyze the current epidemiological SARS-COV-2 situation during the study data provided by the Russian Federal Service on Customers' Rights Protection and Human Well-Being Surveillance and JHU CSSE. Statistical analysis was carried out using RStudio. Results: The study results showed that vaccination coverage of first-year students at the Moscow branch of Sechenov University during the fourth wave of the SARS-COV-2 pandemic was 42,9±5,13%, at the Baku branch - 69,6±5,86%. The lack of reliable information about anticovid vaccines, indicated by a third of all respondents, may largely determine the motivated participation in the vaccination SARS-COV-2 campaign. The role of medical school in imparting knowledge about active SARS-COV-2 immunization to medical students was found to be insignificant. It was shown that the percentage of students willing to recommend SARS-COV-2 vaccination to the people around them and thereby contribute to increasing collective immunity level significantly depends on the percentage of students vaccinated. It was proved that vaccinated students were characterized by significantly greater psychological stability regardless of their study place. Conclusion: Vaccination is not only a good preventive measure against the infection spread but also a significant factor in stabilizing the psycho-emotional state of first-year students, which significantly affects the quality of their educational process and its effectiveness.

Implications of nanotechnology for the treatment of cancer: Recent advances.

The use of nanoparticles dramatically increases the safety and efficacy of the most common anticancer drugs. The main advantages of nano-drugs and delivery systems based on nano-technology are effective targeting, delayed release, increased half-life, and less systemic toxicity. The use of nano-carriers has led to significant improvements in drug delivery to targets compared with traditional administration of these drugs. In this review, the main tendencies in nano-drug formulations as well as factors limiting their use in clinical settings are discussed. Additionally, the current status of approved nano-drugs for cancer treatment is reviewed.

The mystery of claustral neural circuits and recent updates on its role in neurodegenerative pathology.

INTRODUCTION: The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. OBJECTIVE: Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. MATERIALS AND METHODS: A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. RESULTS: Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

Extensive tracheal resection in lung cancer and tuberculosis: a case report.

BACKGROUND: Tracheal bifurcation resection remains the greatest challenge in airway reconstruction, especially with extensive lesions. Additionally, lung cancer and pulmonary tuberculosis comorbidity complicate the chemoradiotherapy treatment due to the TB reactivation. This case describes tracheal resection in a patient with both tuberculosis (TB) and lung cancer. CASE PRESENTATION: The patient was diagnosed with right lung tuberculosis and upper lobe cancer with trachea invasion complicated by hemoptysis. A right pneumonectomy with circular trachea bifurcation resection was performed. Radiotherapy and chemotherapy were not administered to avoid TB reactivation. At 5.5 years post-surgery, there was cancer recurrence that was treated with radiation therapy. At 10 years post-surgery, an invasive squamous-cell carcinoma of a three-segment bronchus on the left was revealed. Radiation therapy and a course of chemotherapy were carried out with almost complete tumor regression. CONCLUSIONS: TB presence should not serve as a basis for the refusal of cancer treatment. Combined treatment may be recommended when the main infection focus in the pulmonary parenchyma is removed during surgery.

Can miRNAs Be Considered as Diagnostic and Therapeutic Molecules in Ischemic Stroke Pathogenesis?-Current Status.

Ischemic stroke is one of the leading causes of death worldwide. Clinical manifestations of stroke are long-lasting and causing economic burden on the patients and society. Current therapeutic modalities to treat ischemic stroke (IS) are unsatisfactory due to the intricate pathophysiology and poor functional recovery of brain cellular compartment. MicroRNAs (miRNA) are endogenously expressed small non-coding RNA molecules, which can act as translation inhibitors and play a pivotal role in the pathophysiology associated with IS. Moreover, miRNAs may be used as potential diagnostic and therapeutic tools in clinical practice; yet, the complete role of miRNAs is enigmatic during IS. In this review, we explored the role of miRNAs in the regulation of stroke risk factors viz., arterial hypertension, metabolic disorders, and atherosclerosis. Furthermore, the role of miRNAs were reviewed during IS pathogenesis accompanied by excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis, neurogenesis, and Alzheimer's disease. The functional role of miRNAs is a double-edged sword effect in cerebral ischemia as they could modulate pathological mechanisms associated with risk factors of IS. miRNAs pertaining to IS pathogenesis could be potential biomarkers for stroke; they could help researchers to identify a particular stroke type and enable medical professionals to evaluate the severity of brain injury. Thus, ascertaining the role of miRNAs may be useful in deciphering their diagnostic role consequently it is plausible to envisage a suitable therapeutic modality against IS.

Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice.

BACKGROUND: Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive. METHODS: Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress. RESULTS: When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1ß and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1ß levels. CONCLUSIONS: It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours.

The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.

INTRODUCTION: Metformin, a biguanide on the WHO's list of essential medicines has a long history of 50 years or more in treating hyperglycemia, and its therapeutic saga continues beyond diabetes treatment. Glucoregulatory actions are central to the physiological effects of metformin; surprisingly, the precise mechanism with which metformin regulates glucose metabolism is not thoroughly understood yet. METHOD: The main aim of this review is to explore the recent implications of metformin in hepatic gluconeogenesis, AMPKs, and SHIP2 and subsequently to elucidate the metformin action across intestine and gut microbiota. We have searched PubMed, google scholar, Medline, eMedicine, National Library of Medicine (NLM), clinicaltrials.gov (registry), and ReleMed for the implications of metformin with its updated role in AMPKs, SHIP2, and hepatic gluoconeogenesis, and gut microbiota. In this review, we have described the efficacy of metformin as a drug repurposing strategy in modulating the role of AMPKs and lysosomal-AMPKs, and controversies associated with metformin. RESULT: Research suggests that biguanide exhibits hormetic effects depending on the concentrations used (micromolar to millimolar). The primary mechanism attributed to metformin action is the inhibition of mitochondrial complex I, and subsequent reduction of cellular energy state, as observed with increased AMP or ADP ratio, thereby metformin can also activate the cellular energy sensor AMPK to inhibit hepatic gluconeogenesis. However, new mechanistic models have been proposed lately to explain the pleiotropic actions of metformin; at low doses, metformin can activate lysosomal-AMPK via the AXIN-LKB1 pathway. Conversely, in an AMPK-independent mechanism, metformin-induced elevation of AMP suppresses adenylate cyclase and glucagon-activated cAMP production to inhibit hepatic glucose output by glucagon. Metformin inhibits mitochondrial glycerophosphate dehydrogenase; mGPDH, and increases the cytosolic NADH/NAD+, affecting the availability of lactate and glycerol for gluconeogenesis. Metformin can inhibit Src homology 2 domain-containing inositol 5-phosphatase 2; SHIP2 to increase the insulin sensitivity and glucose uptake by peripheral tissues. CONCLUSION: In addition, new exciting mechanisms suggest the role of metformin in promoting beneficial gut microbiome and gut health; metformin regulates duodenal AMPK activation, incretin hormone secretion, and bile acid homeostasis to improve intestinal glucose absorption and utilization.

Catalase: A Potential Pharmacologic Target for Hydrogen Peroxide in the Treatment of COVID-19.

BACKGROUND: Acute respiratory distress syndrome in the elderly with COVID-19 complicated by airway obstruction with sputum and mucus, and cases of asphyxia with blood, serous fluid, pus, or meconium in newborns and people of different ages can sometimes cause hypoxemia and death from hypoxic damage to brain cells, because the medical standard does not include intrapulmonary injections of oxygen-producing solutions. The physical-chemical repurposing of hydrogen peroxide from an antiseptic to an oxygen-producing antihypoxant offers hope for the development of new drugs. METHODS: This manuscript is a meta-analysis performed according to PRISMA guidelines. RESULTS: It is shown that replacement of the traditional acidic activity of hydrogen peroxide solutions by alkaline activity with pH 8.4 and heating the solutions to the temperature of +37 - +42 °C allows to repurpose hydrogen peroxide from antiseptics into inhalation and intrapulmonary mucolytics, pyolytics and antihypoxants releasing oxygen. The fact is that warm alkaline hydrogen peroxide solution (WAHPS) in local interaction with sputum, mucus, pus, blood and meconium provides optimal conditions for the metabolism of hydrogen peroxide to oxygen gas under the action of the enzyme catalase, always present in these tissues. It was established that WAHPS liquefies these biological masses due to alkaline saponification of lipid and protein-lipid complexes and simultaneously transforms dense masses into soft oxygen foam due to active enzymatic metabolism of hydrogen peroxide to oxygen gas, the rapidly appearing bubbles of which are formed by the type of "cold boiling" and literally explode these masses. The results of the first experiments showed that inhalation and intrapulmonary injections of WAHPS can significantly optimize the treatment of suffocation and hypoxemia. DISCUSSION: The results showed that catalase, which is found in sputum, mucus, pus, and blood, may be a target for localized WAHPS because this enzyme provides an intensive metabolism of hydrogen peroxide to oxygen gas up to the formation of the cold boiling process. CONCLUSION: These data provide a new perspective way for intrapulmonary drugs and new technologies for the emergency increase of blood oxygenation through the lungs in asphyxia with thick sputum, mucus, pus, meconium and blood.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases.

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

Locus Coeruleus-Norepinephrine System: Spheres of Influence and Contribution to the Development of Neurodegenerative Diseases.

Locus coeruleus is a small bilateral nucleus in the brainstem. It is the main source of norepinephrine (noradrenaline) throughout the central nervous system (about 70% of all norepinephrine in the central nervous system), and, as shown in numerous studies, it is involved in regulating a significant number of functions. The detailed study of the functions of the Locus Coeruleus (LC) and its significance in human life became possible only after the development of histofluorescence methods for monoamines in the 1960s. The widespread locus coeruleus-norepinephrine (LC-NE) projection system regulates the entire central nervous system and modulates sensory processing, motor behavior, arousal, and cognitive processes. Damage to the LC and the associated decrease in norepinephrine levels are involved in a wide range of clinical conditions and pathological processes. Although much about the anatomy and physiology of the LC is currently known, its ultimate role in the regulation of behavior, control of the sleep-wake cycle, stress response, and the development of pathological conditions (such as Alzheimer's disease, dementia, depression, suicidal behavior, chronic traumatic encephalopathy, and Parkinson's disease) is not fully understood. Non-invasive visualization of the LC can be used for differential diagnosis, determining the stage of the disease, and predicting its course. Studying the dysfunction of the LC-norepinephrine system, involved in the pathogenesis of various neurological diseases, may ultimately form the basis for the development of new treatment methods based on the pharmacological elevation of norepinephrine levels. In this review, we will attempt to highlight the key points regarding the structure and function of the Locus Coeruleus, as well as outline the main directions and prospects for its study.

Exploring Pathways for Pain Relief in Treatment and Management of Lumbar Foraminal Stenosis: A Review of the Literature.

BACKGROUND: Lumbar foraminal stenosis (LFS) involves the narrowing of neural foramina, leading to nerve compression, significant lower back pain and radiculopathy, particularly in the aging population. Management includes physical therapy, medications and potentially invasive surgeries such as foraminotomy. Advances in diagnostic and treatment strategies are essential due to LFS's complexity and prevalence, which underscores the importance of a multidisciplinary approach in optimizing patient outcomes. METHOD: This literature review on LFS employed a systematic methodology to gather and synthesize recent scientific data. A comprehensive search was conducted across PubMed, Scopus and Cochrane Library databases using specific keywords related to LFS. The search, restricted to English language articles from 1 January 2000 to 31 December 2023, focused on peer-reviewed articles, clinical trials and reviews. Due to the heterogeneity among the studies, data were qualitatively synthesized into themes related to diagnosis, treatment and pathophysiology. RESULTS: This literature review on LFS analyzed 972 articles initially identified, from which 540 remained after removing duplicates. Following a rigorous screening process, 20 peer-reviewed articles met the inclusion criteria and were reviewed. These studies primarily focused on evaluating the diagnostic accuracy, treatment efficacy and pathophysiological insights into LFS. CONCLUSION: The comprehensive review underscores the necessity for precise diagnostic and management strategies for LFS, highlighting the role of a multidisciplinary approach and the utility of a unified classification system in enhancing patient outcomes in the face of this condition's increasing prevalence.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Experimental Reconstruction of the Optic Nerve with a Sural Nerve Graft: An in Vivo Experimental Study.

BACKGROUND: Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently - restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. METHODS: The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. RESULTS: Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. CONCLUSIONS: Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries.