Nerve Impulses Research Articles

Engineering a high-throughput clone for industrial-scale production of long-acting GLP-1 analogue with retained bio-efficacy.

Type 2 diabetes mellitus (T2DM) and obesity are critical global health issues with rising incidence rates. Glucagon-like peptide-1 (GLP-1) analogues have emerged as effective treatments due to their ability to regulate blood glucose levels and gastric emptying through central nervous signals involving hypothalamic receptors, such as leptin. To address the short plasma half-life of native GLP-1, a C-16 fatty acid was conjugated to lysine in the GLP-1 analogue sequence to enhance its longevity. This study focuses on engineering a high-throughput clone and evaluation of novel GLP-1 analogues with improved bio-efficacy and production yields. Five plasmid models were created using different N-terminal fusion partners and assessed for hydrophobicity, instability index, and isoelectric point. Three optimal plasmid models were selected based on high-valued hydrophobicity, solubility, and partial solubility. These plasmids were constructed with the pET24a vector, incorporating GLP-1 with fusion tags via recombinant DNA technology and transformed into E. coli BL21 DE3 hosts. The proteins were purified through enzyme digestion and chromatography, resulting in a high-yield peptide. The GLP-1 peptide was conjugated with in-house developed fatty acid compound n-Palmitoyl glutamic acid (n-PGA) and purified using C18 column chromatography, achieving a final product yield of 170-190 mg per liter of fermentation culture. Biological activity was confirmed by cyclic adenosine monophosphate (cAMP) generation and 3 T3 cell differentiation assays, showing a 1.5-fold increase in mRNA gene expression with the clone having n-terminal hydrophobic amino acids, thioredoxin-modified tag, and enterokinase cleavage site, indicating high purity and biological potency of the GLP-1 analogue.

Evaluation of hesperidin as a potential larvicide against Culex pipiens with computational prediction of its mode of action via molecular docking

Hesperidin, a natural flavanone glycoside predominantly found in citrus fruits, has gained attention for its wide-ranging biological activities, including potential insecticidal properties. Culex pipiens, commonly known as the northern house mosquito, is a major vector of several human pathogens, such as the West Nile virus and filariasis, making it a key target in the fight against vector-borne diseases. In this study, we evaluated the larvicidal activity of Hesperidin against Culex pipiens larvae, assessing its potential as an alternative to chemical insecticides. Hesperidin demonstrated potent larvicidal effects, with a lethal concentration 50 (LC50) of 570.3 ± 0.04 µg/mL, outperforming the conventional insecticide Chlorpyrifos 588.3 ± 0.28 µg/mL in efficacy. Molecular docking simulations revealed a strong binding affinity between Hesperidin and crucial neuroreceptors in Culex pipiens, particularly acetylcholinesterase (AChE), a key enzyme involved in nerve signal transmission. The interaction between Hesperidin’s hydroxyl groups and the AChE enzyme’s active site suggests that AChE inhibition is the primary mechanism driving Hesperidin’s insecticidal action. These findings position Hesperidin as a promising, environmentally friendly alternative to synthetic insecticides. However, further research is needed to assess its toxicity to non-target organisms and optimize its formulation for broader application in mosquito control.

The Role of Sulfatides in Liver Health and Disease.

Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells. These cells are involved in alcohol-related liver disease (ArLD) and ischemic liver injury and exert anti-inflammatory effects by regulating the activity of pro-inflammatory type I NKT cells. Loss of sulfatides has been implicated in the chronic inflammatory disorder of the liver known as primary sclerosing cholangitis (PSC); bile ducts deficient in sulfatides increase their permeability, resulting in the spread of bile into the liver parenchyma. Previous studies have shown elevated levels of sulfatides in hepatocellular carcinoma (HCC), where sulfatides could act as adhesive molecules that contribute to cancer metastasis. We have recently demonstrated how loss of function of GAL3ST1, a limiting enzyme involved in sulfatide synthesis, reduces tumorigenic capacity in cholangiocarcinoma (CCA) cells. The biological function of sulfatides in the liver is still unclear; however, this review aims to summarize the existing findings on the topic.

Increased Afferent Nerve Firing Is Correlated With the Detection of Bladder Wall Micromotion in a Perfused Ex-Vivo Porcine Model.

Observable autonomous rhythmic changes in intravesical pressure, termed bladder wall micromotion, is a phenomenon that has been linked to urinary urgency, the key symptom in overactive bladder (OAB). However, the mechanism through which micromotion drives urinary urgency is poorly understood. In addition, micromotion is inherently difficult to study in human urodynamics due to challenges distinguishing it from normal cyclic physiologic processes such as pulse rate, breathing, rectal contractions, and ureteral jetting. Therefore, the goal of this study was to create a reproducible model of micromotion using an ex-vivo perfused porcine bladder, as well as to describe the relationship between micromotion and afferent nerve signaling. Porcine bladders were reanimated using ex-vivo perfusion with a physiologic buffer. The pelvic nerve adjacent to the bladder was dissected, grasped with micro-hook electrodes and electroneurogram (ENG) signals were recorded at 20 kHz. Bladders were catheterized and intravesical pressure measurements were taken using a Laborie XT Urodynamics system. Bladders were filled to a fixed volume of 300 mL and control measurements were recorded. The bladders were then washed with 0.001 M carbachol (CCh) solution and refilled to 300 mL to induce micromotion, which was detected as rhythmic changes in intravesical pressure. ENG amplitude was calculated in μV, and nerve firing rate was calculated as number of spikes above baseline threshold per minute. Micromotion was induced by carbachol in 12/25 (48.4%) of trials as rhythmic changes in intravesical pressure after the instillation of carbachol but not in any control period. A fast Fourier transform (FFT) algorithm showed average peak dominant frequency component amplitude was significantly higher during the carbachol period when compared to the control period (0.47 vs. 0.01 cm-H2O, p < 0.0001). Peak waveform frequency (1.13 vs. 1.54 cycles/min, p > 0.05) did not differ between control and carbachol periods. With regard to afferent nerve signaling, normalized average amplitude (0.66 ± 0.24 vs. 0.05 ± 0.08 μV) and firing rate (0.68 ± 0.28 vs. 0.18 ± 0.22 spike/min) for all bladders was significantly greater in the carbachol period when compared to the control period (p < 0.001). Micromotion can be induced using instillation of carbachol in a perfused ex-vivo porcine bladder. Increased afferent nerve firing is observed during periods of micromotion. Thus, micromotion may drive afferent nerve signaling and may potentially contribute to urinary urgency, detrusor overactivity, and OAB. The development of an experimental ex-vivo porcine model for micromotion provides a reproducible method to study bladder micromotion and its potential role in the pathophysiology of urinary urgency and voiding dysfunction.

A REVIEW ARTICLE ON PHYSIOLOGY OF VISION

The visual pathway predominantly travels beneath the cortex for most of its length. Visual signals in the optic nerves may intersect at the chiasma and then proceed through the optic tracts. The term Ayurveda derives from two words: "Ayu," meaning life, and "Ved," signifying knowledge or science. Therefore, "AYURVEDA" as a whole translates to "the science of life." According to Ayurvedic principles, the universe consists of five funda-mental elements. The body maintains an ideal equilibrium of these elements, and any disruption to this balance results in a state of unhealthiness we refer to as illness. The classical texts of Ayurveda provide detailed insights into the physiology of the sense organs, sensation, perception, and the mind's role in the perception process in an exceptional manner. Indriya (sense faculty) serves as the specialized tool that helps the soul in recognizing even the slightest changes in both the external and internal environments. Indriya acts as the essential element that differentiates living entities from non-living ones. The concept of Indriya pancha panchak, introduced by Achar-ya Charaka, delves into both the anatomical and physiological features of the sense organs. The five sensory faculties include sight (chakshurendriya), hearing (shrotrendriya), smell (ghranendriya), taste (rasanendriya), and touch (sparshnendriya). Each sensory faculty is associated with a specific object: sound (shabda) pertains to hearing, touch (sparsha) relates to the tactile sense, color (rupa) corresponds to sight, taste (rasa) is associated with the gustatory sense, and smell (gandha) links with the olfactory sense organ. Every sensory faculty pos-sesses an excess of one material element. Developed from particular material constituents, each specific sense faculty perceives the properties of its corresponding element. The mechanics of how the external world is per-ceived is referred to as the visual process or the physiology of vision. Ayurveda introduces a special concept known as the Tridosha theory. The three fundamental elements of the human body are collectively termed Tridosha (Vata, Pitta, Kapha). The Tridosha governs the physiological and voluntary activities of the body. Ayur-veda elaborates on the physiology of vision by considering the roles of vata and pitta. Pitta encompasses five different types: Ranjak, Pachak, Alochak, Sadhak, and Bhrajak. The "Alochak Pitta" is recognized as the seat of "Drishti." The retinal pigments Rhodopsin, Iodopsin, and Melanin symbolize Alochak Pitta. Alochak pitta is fur-ther categorized into two types: chakshu vaisheshik located in the eye and buddhi vaisheshik found in the brain. There are three stages in this visual process: the light refraction phase, the phase in which light energy is trans-formed into an electrical impulse, and lastly, the peripheral and central neurophysiology involving the geniculate bodies and optic radiations prior to synapsing in the occipital cortex.

In Vivo Imaging of Cobalt-Induced Ocular Toxicity in a Mouse Model.

Cobalt is a trace element, crucial for red blood cell formation and neurological function. Cobalt toxicity is often only diagnosed after severe manifestations, including visual impairment. We aimed to investigate whether optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can effectively detect cobalt-induced ocular toxicity in a murine model. Five wild-type mice (WT, C57Bl6) received daily intraperitoneal cobalt chloride injections for 28 days with a dosage of 12.5 mg/kg. Another 5 WT mice served as controls. After 28 days, all mice underwent manganese contrast-enhanced MRI and OCT examinations. Macroscopic and histological analysis of the enucleated eyes were performed. MRI revealed an increased signal in the optic nerves of injected mice. Anterion OCT provided in vivo visualization of the entire eye, demonstrating incipient cataract formation in the cobalt-injected mice. Both Spectralis domain OCT and Anterion, followed by histological analyses, confirmed preserved retinal structure with decreased thickness in the cobalt-injected group, with only minor neuronal damage and cell loss. Optic nerve analysis demonstrated myelin loss and increased inflammation with high levels of reactive gliosis. This study demonstrates optic neuropathy induced by cobalt toxicity, as shown by increased optic nerve signal on MRI without significant retinopathy. Anterion OCT showed incipient cataracts in the anterior segment.

In silico analysis of novel Triacontafluoropentadec-1-ene as a sustainable replacement for dodecane in fisheries microplastics: Molecular docking, dynamics simulation and pharmacophore studies of acetylcholinesterase activity.

Plastics play an essential role in modern fisheries and their degradation releases micro- and nano-sized plastic particles which further causes ecological and human health hazards through various environmental contamination pathways and toxicity mechanisms, which can cause respiratory problems, cancer, reproductive toxicity, endocrine disruption and neurological effects in humans. This study utilized various bioinformatics tools through multi-step computational analyses to investigate the interactions between prevalent fisheries microplastics and the key protein receptor acetylcholinesterase (AChE), which is associated with neurotoxicity, as it can interfere with nerve impulses and muscle control. Our results indicate that the binding of seven polymers within AChE's active site, with dodecane and polypropylene exhibited highest affinity with hydrogen bonding were observed through Molecular docking of different program (PyRx) and servers (CB-Dock, eDock) then the stability of AChE-dodecane and AChE-polypropylene complexes were observed through MD simulations for 100 ns. Further analysis of dodecane was done by using pharmacophore modelling and virtual screening. The pharmacophore model of dodecane is based on six hydrophobic rings. Using this model, we screened among thousands of substrates form (CMNPD, COCONUT, NPASS, NANPDB, and ZINC) database and identified fifty highly similar candidates that align with dodecane's structure and interaction with acetylcholinesterase (AChE). The compound triacontafluoropentadec-1-ene exhibited highest binding affinity (score: -9.6) which was further confirmed through molecular dynamics for 100 ns. The key finding for this study is triacontafluoropentadec-1-ene as a promising alternative to dodecane, and the study highlights that the integrated in silico framework presents a valuable computational model for guiding future guidelines on environmental safety through prioritizing constituents and accelerated discovery of alternatives. These findings will help us identify the most hazardous plastics through ranking and characterizing the substance for sustainably "greening" fisheries worldwide. The study forecasts the groundwork of these compounds, which may be able to reduce the environmental toxicity of microplastics in future.

Sciatic nerve analysis in thyroid hormone transporter Mct8 and Oatp1c1 knockout mice.

Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) cause Allan-Herndon-Dudley syndrome (AHDS), a severe form of psychomotor retardation with muscle hypoplasia and spastic paraplegia as key symptoms. These abnormalities have been attributed to an impaired TH transport across brain barriers and into neural cells thereby affecting brain development and function. Likewise, Mct8/Oatp1c1 (organic anion transporting polypeptide 1c1) double knockout (M/Odko) mice, a well-established murine AHDS model, display a strongly reduced TH passage into the brain as well as locomotor abnormalities. To which extent the peripheral nervous system (PNS) is affected by combined Mct8/Oat1c1 deficiency has not been addressed. Using the sciatic nerve as a model, we studied the spatiotemporal expression of TH transporters as well as the sciatic thyroidal state, sciatic nerve myelination and function in M/Odko mice by immuno-fluorescence, qPCR, Western Blotting, and electrophysiology. We detected Mct8 protein expression in sciatic nerve axons, whereas Oatp1c1 expression was observed in a subset of endothelial cells early in postnatal development. Absence of Mct8 and Oatp1c1 did not alter the thyroidal state of isolated nerves at P12. Moreover, electrophysiological studies did not disclose any significant alteration in sciatic nerve signal propagation parameters in adult M/Odko mice. Though Schwann cell numbers were similar, Western blot analysis showed a mild form of hypermyelination in adult M/Odko mice. Altogether, our data point to a largely unaffected sciatic nerve structure and function in the absence of Mct8 and Oatp1c1.

Assessment of Lethal Dose and Lethal Time of Diazinon in Swiss Albino Mice

Approximately two thirds of deaths and millions of nonfatal cases are attributed to organophosphorus pesticides (OPP) annually. Diazinon, a prominent member of the OP pesticides, was introduced for both agriculture and public health usages during. For several decades, the compound was among the top pesticides in use in many countries, including Libya. The toxicity of this compound is based on its ability to inhibiting the acetylcholinesterase enzyme (AchE), which is vitally important for normal nerve impulse transmission. This study evaluated the acute toxicity of diazinon through acute exposure testing on female Swiss albino mice. In the acute toxicity test, 72 mice were subcutaneously injected with doses of diazinon ranging from 320 to 480 μL/ kg. Mortality and symptoms were recorded over four days, with the median lethal dose found to be 403.5 μL/kg. Based on the findings, the present study suggests that stringent controls and surveillance must be placed on diazinon and similar chemicals.

Femtomolar hydrogen sulfide detection via hybrid small-molecule nano-arrays

Early disease diagnosis hinges on the sensitive detection of signaling molecules. Among these, hydrogen sulfide (H2S) has emerged as a critical player in cardiovascular and nervous system signaling. On-chip immunoassays, particularly nanoarray-based interfacial detection, offer promising avenues for ultra-sensitive analysis due to their confined reaction volumes and precise signal localization. Beyond the DNA or protein biomolecules array, this work presents a promising hybrid small molecule nano-array for H2S detection, using the power of dual molecules: a dye for fluorescence emission and a quencher with specific H2S reactivity. Upon H2S interaction, the quenched fluorescence reignites, creating an easily detectable array of bright spots. The molecule nano-array sensor shows exceptional responses to H2S over 8 magnitudes of dynamic range from 1 fM to 0.1 μM, with a remarkable detection limit of 1 fM, just using a 10 μL solution. This H2S detection method has the potential to significantly improve bioassay platforms, and the hybrid small-molecule nano-arrays we developed could be a valuable tool for advancing signaling molecule detection.

Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study.

The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer's disease. The potential of various compounds as AChE inhibitors was investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks (ENM and NMA), statistical potentials (CUPSAT and SWOTein), energy frustration (Frustratometer), and volumetric cavity analyses (MOLE and PockDrug). The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases.

Exploring the Role of Axons in ALS from Multiple Perspectives.

Amyotrophic lateral sclerosis (ALS), commonly known as motor neuron disease, is a neurodegenerative disorder characterized by the progressive degeneration of both upper and lower motor neurons. This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients' quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.

Introduction to Herbal Drug Used as a Local Anesthetic

Herbal medications were historically studied for possible uses as local anesthetics since they include natural bioactive components with analgesic and numbing characteristics. Plants such as Echinacea, Capsicum, Corydalis, and Clove have shown promising results in preclinical tests for their capacity to block nerve transmission and relieve pain when applied topically. These herbal medicines frequently interact with the neurological system, either by blocking nerve impulse transmission or by altering the ion channels involved in Pain perception. Herbal local anesthetics have gained popularity as alternatives to synthetic medications since they have been shown to be less harmful and have fewer adverse effects. While herbal medications have benefits, their efficacy, safety, and mechanism of action require additional clinical research to support their use in medical practice. This review investigates the pharmacological features of numerous herbal medicines with local anesthetic effects, highlighting their potential in pain management as well as the difficulties that remain for their clinical application. any herbal remedies contain anesthetic effects. Herbal medicines with local anesthetic qualities include clove, cinchona, datura, thymol, and spilanthes acmella, which are used in medicine and dentistry. However, their potential applications in dentistry have yet to be completely analyzed. Herbal medications have been widely used in traditional medicine for therapeutic purposes, specially as local anesthetics. This review will look at the numerous herbal compounds known for their local anesthetic properties, including their chemical compositions, methods of action, and clinical efficacy

A ROLE OF AYURVEDA IN THE MANAGEMENT OF KARNABADHIRYA (SEN-SORINEURAL DEAFNESS) - A CASE STUDY.

Acharya Sushruta described Badhirya in 28 Karnagata rogas in Shushrut Samhita. [1].Karna Badhirya is a medical problem that is considered a disability in all age groups of people. Hearing impairment among elderly people is a significant issue, and a person with hearing loss may be unable to hear. There is a rise in cases of hearing loss reported post-pandemic among the younger generation, too. Lack of communication makes the person frustrated, lonely, and depressed [2. In the present study, pre-and post-treatment hearing loss was assessed on an audiometry scale. A 45-year-old male came to OPD complaining of decreased hearing capacity and tiredness at the end of the day. Audiometry report showed moderate sensorineural hearing loss in the bilateral ear and treated with Nasya with Madhukadi tail(4) 3 cycles, three cycles of Madhukadi tail Karnapoorana(5) , Sarivadi vati6) 250mg thrice a day with lukewarm water or milk for one month. Pre- and post-audiometry revealed that his hearing capacity improved from moderate to mild in both ears. Sensory neural hearing loss occurs when there is a problem in the sensory apparatus cochlea or the pathway of conduction of nerve impulses to the brain(3). SNHL can be peripheral or central. It can be congenital or acquired. Decreased hearing capacity results from damage to hair cells, which can be managed by Ayurveda treatment nasya, Karnapoorana with Vatashaman chikitsa. With this study, we can treat this type of hearing loss without any surgical intervention and help them live their life better.

Anthranilic Acid-G-Protein Coupled Receptor109A-Cytosolic Phospholipase A2-Myelin-Cognition Cascade: A New Target for the Treatment/Prevention of Cognitive Impairment in Schizophrenia, Dementia, and Aging.

Cognitive impairment is a core feature of neurodevelopmental (schizophrenia) and aging-associated (mild cognitive impairment and Alzheimer's dementia) neurodegenerative diseases. Limited efficacy of current pharmacological treatments warrants further search for new targets for nootropic interventions. The breakdown of myelin, a phospholipids axonal sheath that protects the conduction of nerve impulse between neurons, was proposed as a neuropathological abnormality that precedes and promotes the deposition of amyloid-β in neuritic plaques. The present review of the recent literature and our own pre- and clinical data suggest (for the first time) that the anthranilic acid (AA)-induced activation of microglial-expressed G-protein coupled receptor (GPR109A) inhibits cytosolic phospholipase A2 (cPLA2), an enzyme that triggers the degradation of myelin and consequently attenuates cognitive impairment. The present review suggests that the up-regulation of AA formation is a sex-specific compensatory (adaptive) reaction aimed to prevent/treat cognitive impairment. The AA-GPR109A-cPLA2-myelin-cognition cascade suggests new nootropic interventions, e.g., the administration of pegylated kynureninase, an enzyme that catalyzes AA formation from Kynurenine (Kyn), a tryptophane catabolite; pegylated interferon-alpha; central and peripheral Kyn aminotransferase inhibitors that increase availability of Kyn as a substrate for AA formation; and vagus nerve stimulation. The cascade predicts nootropic activity of exogenous GPR109A agonists that were designed and underwent clinical trials (unsuccessful) as anti-dyslipidemia agents. The proposed cascade might contribute to the pathogenesis of cognitive impairment. Data on AA in neurodegenerative disorders are scarce, and the proposed cascade needs further exploration in pre- and clinical studies.

The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort

Autism spectrum disorder (ASD) comprises neurodevelopmental disorders with wide variability in genetic causes and phenotypes, making it challenging to pinpoint causal genes. We performed whole exome sequencing on a modest, ancestrally diverse cohort of 195 families, including 754 individuals (222 with ASD), and identified 38,834 novel private variants. In 68 individuals with ASD (~30%), we identified 92 potentially pathogenic variants in 73 known genes, including BCORL1, CDKL5, CHAMP1, KAT6A, MECP2, and SETD1B. Additionally, we identified 158 potentially pathogenic variants in 120 candidate genes, including DLG3, GABRQ, KALRN, KCTD16, and SLC8A3. We also found 34 copy number variants in 31 individuals overlapping known ASD loci. Our work expands the catalog of ASD genetics by identifying hundreds of variants across diverse ancestral backgrounds, highlighting convergence on nervous system development and signal transduction. These findings provide insights into the genetic underpinnings of ASD and inform molecular diagnosis and potential therapeutic targets.

Nervous system in colorectal cancer.

A malignant tumor is a complex systemic disease involving the nervous system, which regulates nerve signals. Cancer neuroscience is a field that explores the interactions between tumors and the nervous system. The gastrointestinal tract is a typical peripheral organ with abundant neuroregulation and is regulated by the peripheral, enteric, and central nervous systems (PNS, ENS, and CNS, respectively). The physiological functions of the gastrointestinal tract are maintained via complex neuromodulation. Neuroregulatory imbalance is the primary cause of gastrointestinal diseases, including colorectal cancer (CRC). In CRC, there is a direct interaction between the nervous system and tumor cells. Moreover, this tumor-nerve interaction can indirectly regulate the tumor microenvironment, including the microbiota, immunity, and metabolism. In addition to the lower nerve centers, the stress response, emotion, and cognition represented by the higher nerve centers also participate in the occurrence and progression of CRC. Herein, we review some basic knowledge regarding cancer neuroscience and elucidate the mechanism underlying tumor-nerve interactions in CRC.

"Electrolyte Imbalance in Chronic Kidney Disease: Management Strategies and Approaches to Enhance Quality Of Life

Chronic Kidney Disease (CKD) is a progressive condition characterized by a gradual loss of kidney function, significantly impairing the body's ability to maintain electrolyte and fluid balance. Electrolytes, including sodium, potassium, calcium, phosphorus, and magnesium, play a crucial role in homeostasis, influencing nerve signaling, muscle function, and acid-base equilibrium. In CKD, the diminished renal function disrupts this delicate balance, leading to prevalent and clinically significant electrolyte imbalances. These imbalances contribute to a range of complications, such as cardiovascular disorders, bone disease, and neuromuscular dysfunction, severely impacting patients' overall quality of life (QoL). Management strategies for electrolyte disturbances in CKD include dietary modifications, pharmacological interventions, and advanced therapies like dialysis and kidney transplantation. These approaches aim to stabilize electrolyte levels, prevent complications, and enhance patients' QoL. This review explores the pathophysiology, clinical manifestations, and diagnostic approaches to electrolyte imbalances in CKD, emphasizing evidence-based management strategies and emerging innovations. Addressing these challenges holistically is crucial for improving clinical outcomes and supporting the well-being of individuals living with CKD.

The potential of noninvasive brain stimulation techniques for the treatment of central nervous system demyelinating diseases: a narrative review

Noninvasive brain stimulation techniques have emerged as a promising therapeutic option for various central nervous system demyelinating diseases. Demyelinating diseases represent a group of pathological conditions that impact the central or peripheral nervous system. They are characterized by damage to or loss of the myelin sheath surrounding nerve fibers. This damage to myelin sheaths disrupts nerve signal transmission, leading to a wide range of signs and symptoms associated with neurological impairment. Treatment for demyelinating diseases usually aligns with the specific underlying cause. Noninvasive brain stimulation techniques can affect neuronal electrical activity and glial cell function, suggesting a potential option for intervention. In this narrative review, we explore the potential of noninvasive brain stimulation techniques for the treatment of central nervous system demyelinating disorders. Noninvasive brain stimulation techniques, including transcranial magnetic stimulation, transcranial electrical stimulation, transcranial focused ultrasound stimulation, optogenetic stimulation, low-intensity pulsed ultrasound, and transcranial photobiomodulation, have been shown to potentially intervene in the treatment of demyelinating diseases by affecting the electrical activity of nerve cells and glial cell function. In addition, this review summarizes the applications and mechanisms of noninvasive brain stimulation techniques in the treatment of central nervous system demyelinating diseases and how these techniques promote myelin regeneration and improve disease prognosis. This review also summarizes research advances in noninvasive brain stimulation techniques for the treatment of multiple sclerosis, acute disseminated encephalomyelitis, progressive multifocal leukoencephalopathy, and neuromyelitis optical spectrum disorder. Noninvasive brain stimulation techniques can improve disease symptoms by promoting oligodendrocyte proliferation and differentiation, enhancing myelin regeneration, and modulating immune responses. Although noninvasive brain stimulation techniques have shown potential in the treatment of various neurological disorders, their use in treating demyelinating diseases remains challenging. For example, transcranial focused ultrasound stimulation is a relatively new noninvasive brain stimulation technique with the advantages of high spatial resolution and the ability to stimulate deep brain structures, but its safety and efficacy in clinical applications need to be further investigated. Optogenetic stimulation offers highly precise neuromodulation, but its feasibility in clinical practice is limited by technical and ethical constraints. Overall, noninvasive brain stimulation techniques have significant potential in the treatment of central nervous system demyelinating diseases, but further research is needed to optimize stimulation parameters, improve therapeutic efficacy, and gain insight into their mechanism of action. With the continuous development of technology and in-depth clinical trials, noninvasive brain stimulation techniques are expected to become an effective treatment for central nervous system demyelinating diseases and provide new therapeutic options for such patients.

Peripheral Mechanisms Underlying Bacillus Calmette-Guerin-Induced Lower Urinary Tract Symptoms (LUTS).

Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70-75% of all bladder cancer cases. The standard treatment for high-risk NMIBC involves transurethral tumour resection followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. While BCG immunotherapy is both safe and effective, it frequently leads to the development of lower urinary tract symptoms (LUTS) such as urinary urgency, frequency, dysuria, and pelvic discomfort. These symptoms can significantly diminish patients' quality of life and may result in the discontinuation of BCG treatment, adversely affecting oncological outcomes. Despite the considerable clinical impact of BCG-induced LUTS, the underlying mechanisms remain unclear, hindering the implementation or development of effective treatments. This review provides novel insights into the potential mechanisms underlying BCG-induced LUTS, focusing on the integrated roles of afferent and efferent nerves in both normal and pathological bladder sensation and function. Specifically, this review examines how the body's response to BCG-through the development of inflammation, increased urothelial permeability, and altered urothelial signalling-might contribute to LUTS development. Drawing from known mechanisms in other common urological disorders and data from successful clinical trials involving NMIBC patients, this review summarises evidence supporting the likely changes in both sensory nerve signalling and bladder muscle function in the development of BCG-induced LUTS. However, further research is required to understand the intricate mechanisms underlying the development of BCG-induced LUTS and identify why some patients are more likely to experience BCG intolerance. Addressing these knowledge gaps could have profound implications for patients' quality of life, treatment adherence, and overall outcomes in NMIBC care.