Therapeutic Approaches Research Articles

Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans.

Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

Validity of the Triglyceride-Glucose Indices for Predicting the Severity of Coronary Artery Disease in Patients With Nondiabetic Chronic Coronary Syndrome.

The triglyceride-glucose (TyG) index was shown to be an independent predictor of coronary artery disease (CAD) progression and prognosis. However, whether the TyG index can predict the severity of CAD in nondiabetic patients with chronic coronary syndrome remains unclear. A total of 118 individuals who underwent elective coronary angiography were classified into group A (59 with coronary lesions) and group B (59 with normal coronary arteries; as a control group) after coronary angiography and laboratory tests for fasting and the postprandial (PP) TyG index. The complexity of CAD was determined by the Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score >22 indicated moderate-high risk), and patients diagnosed with diabetes or prediabetes were excluded. The TyG index was not related to the SYNTAX score in groups A and B; however, in the CAD group with an low-density lipoprotein (LDL) concentration <70 mg/dL (group A1), a fasting TyG index ≥8.25 and a PP TyG index ≥11 could predict moderate-high SYNTAX risk score; in addition, the odds ratio (OR) was 4.3× higher and the relative risk (RR) was 1.8× greater (OR = 4.3, RR = 1.8, 95% confidence interval = 1.4-13.5, P < 0.05) for individuals with a higher fasting TyG index ≥8.25 to have a moderate-high SYNTAX risk score. Individuals with a higher PP TyG index ≥11 had OR of 2.6× higher and a RR of 1.4× greater to have moderate-high SYNTAX risk score. Both fasting and PP TyG levels were associated with greater coronary anatomical complexity (SYNTAX score >22) in nondiabetic chronic coronary patients with LDL <70 mg/dL. Fasting and the PP TyG indices can serve as noninvasive predictors of CAD complexity in nondiabetic patients with LDL <70 mg/dL and could change the management and therapeutic approaches.

Neuronal Vulnerability to Degeneration in Parkinson's Disease and Therapeutic Approaches.

Parkinson's disease is the second most common neurodegenerative disease affecting millions of people worldwide. Despite the crucial threat it poses, currently, no specific therapy exists that can completely reverse or halt the progression of the disease. Parkinson's disease pathology is driven by neurodegeneration caused by the intraneuronal accumulation of alpha-synuclein (α-syn) aggregates in Lewy bodies in the substantia nigra region of the brain. Parkinson's disease is a multiorgan disease affecting the central nervous system (CNS) as well as the autonomic nervous system. A bidirectional route of spreading α-syn from the gut to CNS through the vagus nerve and vice versa has also been reported. Despite our understanding of the molecular and pathophysiological aspects of Parkinson's disease, many questions remain unanswered regarding the selective vulnerability of neuronal populations, the neuromodulatory role of the locus coeruleus, and alpha-synuclein aggregation. This review article aims to describe the probable factors that contribute to selective neuronal vulnerability in Parkinson's disease, such as genetic predisposition, bioenergetics, and the physiology of neurons, as well as the interplay of environmental and exogenous modulators. This review also highlights various therapeutic strategies with cell transplants, through viral gene delivery, by targeting α -synuclein and aquaporin protein or epidermal growth factor receptors for the treatment of Parkinson's disease. The application of regenerative medicine and patient-specific personalized approaches have also been explored as promising strategies in the treatment of Parkinson's disease.

Hematopoietic Stem-Cell Transplantation: Exploring the Latest Advances and Gaps in Disparities, Psychosocial and Symptom Management Interventions, and Chronic Graft-Versus-Host Disease Care.

Although allogeneic hematopoietic cell transplantation (HCT) offers a potential for cure for many patients with advanced hematologic malignancies and bone marrow failure or immunodeficiency syndromes, it is an intensive treatment and accompanied by short- and long-term physical and psychological symptoms requiring specialized care. With substantial advances in therapeutic approaches for HCT and supportive care, HCT survivors experience less morbidity and mortality. However, disparities in both HCT access and outcomes persist, and HCT survivors and their caregivers often lack access to much-needed psychosocial care. Additionally, more medical and psychosocial resources are needed to holistically care for HCT survivors with chronic graft-versus-host disease (GVHD). Hence, this chapter focuses on three areas pertaining to advances and gaps in HCT care: disparities in access to and outcomes of HCT, psychosocial and physical symptom management with supportive care interventions, and GVHD prevention and management.

Innovative Therapeutic Approaches in Congenital Myasthenic Syndromes.

To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.

LncRNA NORAD alleviates dysfunction of renal proximal tubular epithelial cells during the sepsis-associated acute kidney injury by modulating the miR-155-5p-PDK1 axis.

The sepsis-associated acute kidney injury (Sa-AKI) is closely related to high mortality rates worldwide. Injury to the renal proximal tubular epithelial cells (RPTECs), caused by pathological conditions, is a major cause of acute kidney injury (AKI). The lncRNA NORAD has been reported to be positively associated with kidney cancers. However, the biological roles and underlying mechanisms of NORAD in RPTECs during AKI are still unclear. In this study, we found that NORAD was significantly downregulated in RPTECs from AKI tissues. Overexpression of NORAD alleviated RPTECs injury induced by lipopolysaccharide (LPS). Additionally, glucose metabolism was significantly impaired during AKI, and LPS treatment inhibited glucose metabolism in RPTECs. We demonstrated that NORAD rescued the LPS-induced inhibition of glucose metabolism in RPTECs. Furthermore, miRNA-155-5p was significantly upregulated in RPTECs from AKI. Through bioinformatics analysis, RNA pull-down, RNA IP, and luciferase assays, we showed that NORAD directly associated with miR-155-5p to downregulate its expression. Moreover, overexpression of miR-155-5p inhibited glucose metabolism by directly targeting the 3'UTR of the glucose metabolism enzyme, pyruvate dehydrogenase kinase 1 (PDK1). Finally, rescue experiments validated that NORAD's protective effect on RPTECs injury was mediated through modulation of the miR-155-5p-PDK1-glucose metabolism pathway. In summary, these results reveal that lncRNA NORAD can alleviate RPTECs dysfunction by targeting the miR-155-5p-PDK1 axis, suggesting that NORAD has the potential to contribute to the development of therapeutic approaches against Sa-AKI.

Altering plasma lipids and liver enzyme activities via hippocampal injections of hen Lysozyme amyloid aggregates in an Alzheimer's disease mouse model: Insights into the therapeutic role of Bis (Indolyl) phenylmethane.

Alzheimer's disease (AD) is a prevalent form of dementia in the elderly. There is currently no effective treatment available for this disease. Diagnosis of AD typically relies on clinical manifestations and specific biomarkers. The present study investigated the impact of inducing Alzheimer's disease (AD) in mice through the injection of lysozyme amyloids formed in the presence or absence of Bis (Indolyl) phenylmethane (BIPM) on alterations in plasma lipid profiles and liver enzyme activities. 24 adult Wistar rats were divided into control, Scopolamine, Lysozyme, BIPM groups and the blood samples were obtained from the groups for biochemical analysis. The findings of the study revealed significant changes in the plasma lipid profiles and liver enzyme markers of the Lysozyme group compared to the control group. The Lysozyme group exhibited elevated triglycerides (n=6, P<0.02) and LDL levels (n=6, P<0.02), reduced HDL (n=6, P<0.05) and cholesterol levels (n=6, P<0.02), and altered serum glutamic oxaloacetic transaminase (SGOT) level (n=6, P<0.05) compared to controls. While the level of serum glutamic pyruvic transaminase (SGPT) did not change significantly compared to the control. BIPM groups showed no significant changes in lipid or enzyme levels compared to controls. Overall, our research has shown that BIPM has the ability to modify the structure of HEWL aggregates, thereby improving the detrimental effects associated with AD caused by these aggregates. Analyzing lipid profiles and liver enzyme markers presents a promising avenue for targeted therapeutic approaches. These alterations observed in the plasma may potentially serve as candidate biomarkers for diagnosing this disease.

Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.

Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma.

The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. A high throughput liquid chromatography-tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment-resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient-derived organoid (PDO) assays. A multiomics profiling of 8536 high-confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment-resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5-lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

Postpartum depression: Impact on pregnant women and the postnatal physical, emotional, and cognitive development of their children. An ecological perspective.

Maternal mental health problems during pregnancy, childbirth, and the postpartum period are a challenge for public health. Not recognizing them hinders a timely diagnosis and treatment and has an impact on the mother and the establishment of the fundamental bond of the mother-child dyad. We must recognize the risk factors (age, socioeconomic status, mental health history, family dysfunction, unfavorable environment), clinical manifestations, and screening tools. There is evidence that the effect of stress, anxiety, and depression during pregnancy negatively affect fetal neurodevelopment and condition child developmental outcomes. Here we describe the negative impact of postpartum depression during the first months of life, which affects mother-child bonding, postnatal development (emotional, behavioral, cognitive, language), and the maintenance of breastfeeding. We also recognize protective factors that mitigate its effects. It is essential to establish preventive strategies and interdisciplinary diagnostic and therapeutic approaches to minimize the risks to the mother and her children.

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL1, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model.The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2Х3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2Х3-DOPE-DSPE-PEG2000 (0.62 % mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL1) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

Unveiling the functional food properties of Pepromia pellucida: Phytochemical profiling, antioxidative potential, and their nanoemulsion fraction in wound healing efficacy

Peperomia pellucida, a tropical plant belonging to the Piperaceae family, has long been recognized for its potential medicinal properties, including anti-inflammatory, analgesic, and antimicrobial effects. This study investigates the efficacy of Peperomia pellucida nanoemulsion (PPNE) as a novel therapeutic approach for improving burn wound healing in Wistar rats. The nanoemulsion was formulated using the high-energy ultrasonication method, optimized for droplet size, polydispersity index, and stability. A 30% burn wound was induced on the dorsum of 60 Wistar rats, which were then divided into three groups: control (untreated), silver sulfadiazine (SSD) treated, and PPNE treated. Inflammatory cytokine levels (TNF-α, IL-6, and IL-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that PPNE treatment significantly accelerated wound closure rates compared to both control and SSD-treated groups, with complete wound closure achieved by day 10 in the PPNE-treated group. Histopathological examination revealed improved re-epithelialization, granulation tissue formation, and collagen deposition in the PPNE group compared to the control and SSD groups. Additionally, PPNE treatment significantly reduced inflammatory cytokine levels and enhanced antioxidant enzyme activities, suggesting a reduction in inflammation and oxidative stress in the treated wounds. In conclusion, this study demonstrates the potential of P. pellucida nanoemulsion as a promising and effective therapeutic approach for improving burn wound healing. The observed enhanced wound healing properties may be attributed to the combined anti-inflammatory, antioxidant, and antimicrobial effects of the PPNE, warranting further investigation and potential clinical application.

Curing Stage IV Melanoma: Where Have We Been and Where Are We?

Little more than 10 years ago, metastatic melanoma was considered to have one of the poorest cancer outcomes, associated with a median overall survival of 6-8 months. Cytotoxic chemotherapy offered modest response rates of 20%-30%, but no clear survival benefit. Patients were routinely enrolled in clinical trials as their first-line therapy in the search for effective novel therapeutics. Remarkable developments in molecular biology, cancer genomics, immunology, and drug discovery have dominated the early part of the 21st century, and nowhere have the benefits been better realized than in the transformation of outcomes for patients with metastatic melanoma: since 2011, 14 new agents have been approved that significantly increase survival, with long-term remissions and, possibly now, potential for cure. Even so, there is still much work to be done, given that most treated patients still die of their disease. Although most survival gains have so far been realized for cutaneous melanoma, improving treatment options for those 10% of patients with rarer, noncutaneous melanomas is a high priority. Key novel therapeutic approaches aimed at improving outcomes with potential for curing patients with melanoma are considered.

Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances.

Renal cell carcinoma (RCC) is one of the 10 most commonly diagnosed solid tumors. Most RCCs are histologically defined as clear cell, comprising approximately 75% of diagnoses. However, the remaining RCC cases are composed of a heterogeneous combination of diverse histopathologic subtypes, each with unique pathogeneses and clinical features. Although the therapeutic approach to both localized and metastatic RCCs has dramatically changed, first with the advent of antiangiogenic targeted therapies and more recently with the approval of immune checkpoint inhibitor (ICI)-based combinations, these advances have primarily benefited the clear cell RCC patient population. As such, there remains critical gaps in the optimization of treatment regimens for patients with non-clear cell, or variant, RCC histologies. Herein, we detail recent advances in understanding the biology of RCC with variant histology and how such findings have guided novel clinical studies investigating precision oncology approaches for these rare subtypes. Among the most common variant histology RCCs are papillary RCC, comprising approximately 15%-20% of all diagnoses. Although a histopathologically diverse subset of tumors, papillary RCC is canonically associated with amplification of the MET protooncogene; recently completed and ongoing trials have investigated MET-directed therapies for this patient population. Finally, we discuss the unique biology of RCC with sarcomatoid dedifferentiation and the recent clinical findings detailing its paradoxical sensitivity to ICIs.

High Mobility Group Box 1 Protein: A Plausible Therapeutic Molecular Target in Parkinson's disease.

Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.

Brain N -acetyl-aspartyl-glutamate is associated with cognitive function in older virally suppressed people with HIV.

Cognitive impairment persists in virally suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N -acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease. Inhibition of GCPII increases brain NAAG and improves learning and memory in rodent and primate models. As higher order cognitive impairment is present in VS-PWH, and NAAG has not been investigated in earlier magnetic resonance spectroscopy studies (MRS), we investigated if brain NAAG levels measured by MRS were associated with cognitive function. We conducted a retrospective analysis of 7-Tesla MRS data from a previously published study on cognition in older VS-PWH. The original study did not separately quantify NAAG, therefore, work for this report focused on relationships between regional NAAG levels in frontal white matter (FWM), left hippocampus, left basal ganglia and domain-specific cognitive performance in 40 VS-PWH after adjusting for confounds. Participants were older than 50 years, negative for affective and neurologic disorders, and had no prior 3-month psychoactive-substance use. Higher NAAG levels in FWM were associated with better attention/working memory. Higher left basal ganglia NAAG related to better verbal fluency. There was a positive relationship between hippocampal NAAG and executive function which lost significance after correction for confounds. These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH.

Assessment of clinical symptoms and pathological effects of degenerative arthritis in rats

Degenerative arthritis, particularly affecting the knee joint, is a prevalent condition in Taiwan. While milder cases may only result in slight discomfort during walking, severe cases can lead to significant mobility issues and even loss of basic movement capabilities. Unfortunately, once articular cartilage is lost due to degenerative arthritis, it cannot be regenerated. Currently, the severity of knee joint degeneration is classified into primary, intermediate, and severe stages, which guides the selection of treatment options. These treatments range from non-surgical interventions to surgical procedures. Given the significance of preventing knee joint degeneration, researchers have been exploring various methods. One such approach involves establishing animal models to mimic degenerative arthritis conditions in humans. In this study, researchers utilized anterior cruciate ligament transection (ACLT) combined with medial meniscectomy (MMx) surgery to create a rat model of degenerative arthritis. The successful establishment of this model provides a valuable tool and assessment of clinical symptoms and pathological effects of degenerative arthritis in rats for studying potential drugs and designing therapeutic strategies for degenerative arthritis. By leveraging this rat model, researchers can investigate the efficacy of different pharmaceutical interventions and therapeutic approaches. This could ultimately lead to the development of novel treatments for degenerative arthritis, benefiting individuals suffering from this debilitating condition.

GARLIC: Nature's potent antifungal and antibacterial ally - cream formulation and evaluation

In the pursuit of effective and safe treatments for infectious diseases, herbal remedies have garnered significant attention due to their diverse phytochemical composition and potential therapeutic properties. This study aimed to explore the phytochemical profile and evaluate the antibacterial and antifungal properties of herbal garlic extracts. Traditional natural products continue to be sought after for their bioactive compounds, which offer promising avenues for therapeutic intervention in both human and veterinary medicine. Our investigation not only sheds light on the regional variation of stomach disease occurrence, highlighting the role of dietary factors, but also underscores the importance of herbal preparations in medicinal practice. By combining various plant classes, herbal formulations can exert localized effects upon application, penetrating the skin or mucous membranes to target underlying conditions. The effectiveness of these combined medications may lie in their synergistic mechanisms, offering a comprehensive therapeutic approach. This research contributes valuable insights into the potential of herbal remedies as adjuncts or alternatives to conventional treatments, paving the way for further exploration in infectious disease management and prevention strategies.

Review on therapeutic approach of anti-acne treatment by Azadirachta indica and Ocimum gratissimum

Review on therapeutic approach of anti-acne treatment by Azadirachta indica and Ocimum gratissimum

The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.

Chronic pain represents a prevalent and costly medical challenge globally. Nicotinic acetylcholine receptors (nAChRs), one type of ligand-gated ion channels found extensively in both the central and peripheral nervous systems, have emerged as promising therapeutic targets for chronic pain. Although there are currently no FDA-approved analgesics specifically targeting nAChRs, accumulating preclinical and clinical evidence suggest that selective ligands for alpha 7 (α7) nAChRs show potential for treating chronic pain, boasting a reduced incidence of side effects compared with other nicotinic receptor types. The recent structural resolution of human α7 nAChRs has confirmed their negative association with heightened pain, providing a valuable foundation for the development of targeted medications. This review presents a comprehensive overview, encompassing insights into the roles of α7 nAChRs derived from structural and functional studies, recent advancements in pharmacology, and investigations into their involvement in the pathophysiology of chronic pain. Moreover, the review addresses the variability in analgesic effects based on the type of receptor agonist and highlights the current research limitations. As such, this review offers potential therapeutic approaches for the development of innovative strategies for chronic pain management.