Therapeutic Applications Research Articles

NADPH Oxidases in Neurodegenerative Disorders: Mechanisms and Therapeutic Opportunities.

The NADPH oxidase (NOX) enzyme family, located in the central nervous system (CNS), is recognized as a source of reactive oxygen species (ROS) in the brain. Despite its importance in cellular processes, excessive ROS generation leads to cell death and is involved in the pathogenesis of neurodegenerative disorders. NOX enzymes contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke, highlighting their potential as targets for future therapeutic development. This review will discuss NOX's contribution and therapeutic targeting potential in neurodegenerative diseases, focusing on PD, AD, ALS, and Stroke. Homeostatic and physiological levels of ROS are crucial for regulating several processes, such as development, memory, neuronal signaling, and vascular homeostasis. However, NOX-mediated excessive ROS generation is deeply involved in the damage of DNA, proteins, and lipids, leading to cell death in the pathogenesis of a wide range of diseases, namely neurodegenerative diseases. It is essential to understand the role of NOX homologs in neurodegenerative disorders and the pathological mechanisms undergoing neurodegeneration mediated by increased levels of ROS. This further knowledge will allow the development of new specific NOX inhibitors and their application for neurodegenerative disease therapeutics.

Synthesis and Biological Activity of Pyrrolizidine Alkaloids: A Review

Abstract: Pyrrolizidine alkaloids (PAs) belong to a structurally varied class of natural products that have garnered significant attention due to their intriguing chemical properties and broad range of biological activities. This review aims to provide a comprehensive overview of the synthesis and biological activity of pyrrolizidine alkaloids. An in-depth exploration of the various synthetic methodologies employed in the construction of these complex molecules, including classical and modern synthetic approaches, is presented in this review. Moreover, the potential therapeutic applications of these alkaloids are discussed, emphasizing their promising role in drug discovery and development. By synthesizing the current knowledge, this paper aims to facilitate further research in the field and inspire the discovery of novel bioactive compounds with therapeutic potential.

Current Expansion of Silver and Gold Nanomaterials towards Cancer Theranostics: Development of Therapeutics

Abstract: Nanomaterial-based therapeutics is an emerging tool for the treatment of numerous types of cancer. Various types of polymeric, lipid and inorganic nanoparticles (NPs) result in a wider series of applications in cancer diagnosis and therapeutics. The NPs properties are due to high surface area to volume ratio, surface plasmon resonance, absorption in the visible spectrum and light scattering. These unique characteristics of NPs arise due to their optical surface properties for conjugation/surface modification and smaller size. In cancer therapeutics, NPs based products are used as a biomarker for early detection/diagnosis of tumours, drug nano-conjugates for the delivery of chemotherapeutic drugs to the tumour-specific site, chemo-protective agents, etc. : Furthermore, other advantages of NPs are biocompatibility, lesser toxicity, enhanced permeability and retention effect, higher stability, and specific targeting with a selective accumulation of nano drugs in the tissue of the tumour. The selective targeting of NPs to tumour tissue is possible by adding surface-active targeting agents i.e., antibodies. The selective transport of drug NPs conjugates to the cancer cells is increased and extravagated due to permeable vasculature from endothelial cells gap while failing the transport of drug NPs conjugates in normal cells. This review emphasizes metallic NPs, including silver NPs (AgNPs) and gold NPs (AuNPs), which are extensively reconnoitered in various applications in cellular targeting, imaging, drug delivery, DNA-NPs conjugates for biosensor/point of care devices development, photothermal/photodynamic therapy, protein-protein interaction, etc. In addition, this review discussed different synthetic methods of AgNPs and AuNPs and characterization methods. Furthermore, it highlighted the different properties and applications of AgNPs and AuNPs in cancer theranostics.

Neuroendocrinological and Clinical Aspects of Leptin.

Obesity is characterized by an abnormal increase in adipose tissue mass and is regarded as a neurobehavioral as well as a metabolic disorder. Increases in body fat are caused by even slight, long-term discrepancies between energy intake and energy expenditure. It is a chronic condition linked to the metabolic syndrome, a spectrum of risky conditions, such as diabetes, high blood pressure, and heart disease. With a swiftly rising prevalence, obesity has emerged as a significant global health concern. Leptin influences the brain's neuroendocrine and metabolic processes, which is important for maintaining energy homeostasis. White adipose tissue secretes the majority of leptin, and there is a positive correlation between leptin levels in the blood and body fat percentages. The central nervous system is also modulated by leptin levels to modify energy intake and usage. The idea of an obesity cure sparked excitement after it was discovered more than 25 years ago. However, the leptin medication only effectively reduces weight in patients with congenital leptin insufficiency and not in patients with typical obesity who may also have leptin resistance. Recent research has focused on the role of leptin in managing weight reduction and preventing "yo-yo dieting." This review concentrates on the neurological effects of leptin with a focus on therapeutic and diagnostic applications, particularly for childhood obesity.

SiRNA Mediated Downregulation of RhoA Expression Reduces Oxidative Induced Apoptosis in Retinal Ganglion Cells.

Glaucoma is the second leading cause of blindness. Apoptosis of retinal ganglion cells (RGCs) is an important mechanism of glaucomatous optic injury. Rho kinase expression is significantly increased in apoptotic RGCs. This study aimed to investigate the role of RhoA, a Rho GTPase, on the survival of RGCs and further to explore its potential therapeutic applications. RGCs were treated with siRhoA for 24 hours in vitro. Knockdown of RhoA was confirmed with quantitative RT-PCR. Oxidative stress was induced by treating the RGCs with 200 μM of H2O2 for 1 hour, and apoptosis of RGCs was quantified with TUNEL assay in situ, and with flow cytometry. The mRNA expression levels of RhoA, Nogo receptor, caspase 3 and Bcl-2 were evaluated by quantitative RT-PCR, and the protein levels of RhoA, ROCK1, ROCK2, Nogo receptor, caspase 3 and Bcl-2 were evaluated by Western blot. We found siRhoA treatment efficiently downregulated the expression of RhoA in RGCs and protected against H2O2-induced injury in RGCs in vitro. Apoptosis of RGC cells under oxidative stress was quantified in situ using TUNEL assay and confirmed with flow cytometry (FCM). With the knockdown of RhoA, the expression of ROCK1, ROCK2, Nogo Receptor, Casepase-3 were decreased, while the expression of Bcl-2 was increased in both mRNA and protein level. Our data indicated that siRhoA prevented H2O2-induced apoptosis in RGC cells by modulating the RhoA/ROCK pathway. The results suggested that siRhoA may exert potentially effective neuroprotection for RGCs by reducing injury.

Purinergic Signaling and its Role in the Stem Cell Differentiation.

Purinergic signaling is a mechanism in which extracellular purines and pyrimidines interact with specialized cell surface receptors known as purinergic receptors. These receptors are divided into two families of P1 and P2 receptors, each responding to different nucleosides and nucleotides. P1 receptors are activated by adenosine, while P2 receptors are activated by pyrimidine and purines. P2X receptors are ligand-gated ion channels, including seven subunits (P2X1-7). However, P2Y receptors are the G-protein coupled receptors comprising eight subtypes (P2Y1/2/4/6/11/12/13/14). The disorder in purinergic signaling leads to various health-related issues and diseases. In various aspects, it influences the activity of non-neuronal cells and neurons. The molecular mechanism of purinergic signaling provides insight into treating various human diseases. On the contrary, stem cells have been investigated for therapeutic applications. Purinergic signaling has shown promising effect in stem cell engraftment. The immune system promotes the autocrine and paracrine mechanisms and releases the significant factors essential for successful stem cell therapy. Each subtype of purinergic receptor exerts a beneficial effect on the damaged tissue. The most common effect caused by purinergic signaling is the proliferation and differentiation that treat different health-related conditions.

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications.

Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer. This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.

Revolutionizing Infection Control: Harnessing MXene-Based Nanostructures for Versatile Antimicrobial Strategies and Healthcare Advancements.

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare.

A Panorama of Extracellular Vesicle Applications: From Biomarker Detection to Therapeutics.

Extracellular vesicles (EVs) secreted by all cell types are involved in the cell-to-cell transfer of regulatory factors that influence cell and tissue phenotypes in normal and diseased tissues. EVs are thus a rich source of biomarker targets for assays that analyze blood and urinary EVs for disease diagnosis. Sensitive biomarker detection in EVs derived from specific cell populations is a key major hurdle when analyzing complex biological samples, but innovative approaches surveyed in this Perspective can streamline EV isolation and enhance the sensitivity of EV detection procedures required for clinical application of EV-based diagnostics and therapeutics, including nanotechnology and microfluidics, to achieve EV characterizations. Finally, this Perspective also outlines opportunities and challenges remaining for clinical translation of EV-based assays.

Therapeutic Potential of Piperine: A Comprehensive Review

Abstract: Piperine, an alkaloid from black pepper, has demonstrated diverse pharmacological properties and potential therapeutic applications. Piperine content varies with the pepper plant and ranges from 2 to 7.4% in black pepper. Piperine possesses remarkable biological properties, including antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, and hepatoprotective qualities. Its ability to affect numerous signaling pathways and biological targets implicated in disease development is responsible for these functions. Studies have shown piperine to have high antioxidant activity, which aids in reducing oxidative stress and preventing cellular damage. It has been established that its anti-inflammatory effects suppress the generation of pro-inflammatory mediators, thereby relieving inflammation-related diseases. This review emphasizes and examines piperine's medical and health-promoting benefits and proposed mechanisms of action in health promotion and illness prevention.

Targeted Degradation of Cell-Surface Proteins via Chaperone-Mediated Autophagy by Using Peptide-Conjugated Antibodies.

Cell-surface proteins are important drug targets but historically have posed big challenges for the complete elimination of their functions. Herein, we report antibody-peptide conjugates (Ab-CMAs) in which a peptide targeting chaperone-mediated autophagy (CMA) was conjugated with commercially available monoclonal antibodies for specific cell-surface protein degradation by taking advantage of lysosomal degradation pathways. Unique features of Ab-CMAs, including cell-surface receptor- and E3 ligase-independent degradation, feasibility towards different cell-surface proteins (e.g., epidermal growth factor receptor (EGFR), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2)) by a simple change of the antibody, and successful tumor inhibition in vivo, make them attractive protein degraders for biomedical research and therapeutic applications. As the first example employing CMA to degrade proteins from the outside in, our findings may also shed new light on CMA, a degradation pathway typically targeting cytosolic proteins.

Silver Nanoparticles as Antiviral and Antibacterial Agents: A Comprehensive Review of Synthesis Methods and Therapeutic Application

AbstractSilver nanoparticles have shown inhibitory capabilities and its use in battling viral infections are strengthened by its potent antibacterial activity. Notably, since it directly affects antiviral efficacy, the proper choice of synthesis process for making silver nanoparticles is a vital element to be taken into consideration. The synthesis of silver nanoparticles for the treatment of viral and bacterial infections involves creating silver particles at the nanoscale with unique antimicrobial properties. Various methods exist for synthesizing silver nanoparticles, including chemical reduction, green synthesis, and physical methods. Chemical reduction involves using reducing agents to convert silver ions into silver nanoparticles. Green synthesis employs reducing agents in an environmentally friendly manner. Physical methods rely on techniques such as laser ablation or thermal evaporation to produce silver nanoparticles. In order to provide technological guidance for choosing antiviral silver nanoparticle manufacturing methods, this paper introduces and explores alternative synthesis methods for creating silver nanoparticles.

Temperature/pH/reduction-sensitive multiple stimulus-responsive nanogels synthesized by one-pot method for design as curcumin carriers

Curcumin (Cur) is of interest due to its widely reported pharmacology, which is limited by its low water solubility and low bioavailability of clinical use. Here, we report the characterization and application of a multiple stimulus-responsive nanogel loaded with Cur. Sensitive P(AM-co-NIPAM) nanogels for pH, temperature, and reduction stimuli were prepared by reflux precipitation polymerization method using AM and NIPAM as raw materials. DLS and SEM analyses showed that the fabricated nanogels had a uniform size distribution with spherical and nucleated-shell structures. By adjusting the feeding amounts of reactive monomers, cross-linkers, and initiators, a series of monodisperse nanogels with different particle sizes could be obtained. The representative nanogels have different Cur-loaded behaviors at different temperatures, times, and initial concentrations of the drug, as well as a sensitive release to changes in pH, temperature, or reducing conditions. Cur-P(AM-co-NIPAM) nanogels showed superior antioxidant activity over the free Cur in vitro. Meanwhile, it inhibited LPS and H2O2-induced oxidative stress, which could effectively inhibit the cellular production of excessive reactive oxygen species and had a protective effect against LPS-induced cellular damage. This nanogel controlled release system significantly improved the safety limit of Cur without hemolytic behavior and had good cytocompatibility. The successful development of such Cur nanogels will lead to advanced materials that can be functionalized and optimized for the controlled delivery of small molecules or biomolecules for targeted therapeutic and biomedical applications.

Copper and Copper Complexes in Tumor Therapy.

Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement in cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential for maintaining copper homeostasis, as imbalances can lead to toxicity and cell death. The development of drugs that target copper homeostasis has emerged as a promising strategy for anticancer treatment, with a particular focus on copper chelators, copper ionophores, and novel copper complexes. Recent research has also investigated the potential of copper complexes in cancer therapy.

Real-time dynamic analysis of EEG Response for Live Indian Classical Vocal Stimulus with Therapeutic Indications

Numerous studies have been conducted on the connection between music and the brain, and it has been established that listening to music directly affects brain activity and stimulation. The potential benefits of music therapy, which uses music as a tool for healing and fostering well-being, have come to light in a number of circumstances. However, there is a gap in understanding the effects of Indian classical music (ICM) on the brain and its therapeutic applications. Yaman and Puria Dhanashree were the two chosen ragas, which share same notes (swaras) and differs in two of their counter notes. The brain responses are captured from five volunteers through 24 channel Electroencephalogram (EEG) cap using a smartphone, which is utilized to allocate electrodes to different regions of the brain. In this work, different automated approaches for identifying brain regions evoked to live ICM stimuli are proposed, considering input and output uncertainties. These approaches are based on automated energy and Mahalanobis distance measurements, and, a region-specific real-time algorithm based on eigen perturbation, which provides a measure to capture the time evolution of brain activity. This identification is relevant in understanding dynamic changes in brain responses during musical experiences providing a more comprehensive perception and processing of ICM in the human brain. Also, significant change in beta band power reduction was observed after music. These approaches can help integrate it into evidence-based music therapy for cognitive, emotional, and psychological conditions. The findings of this study provide evidence indicating ragas activate different brain regions based on listener’s musical knowledge and is a first step for mhealth based applications.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity

Abstract Purpose Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. Methods RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. Results Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (−16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug’s characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid’s ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 μM for free RES to 0.5 ± 0.033 μM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 μMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 μM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. Conclusion Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

A comparative study on biosynthesized silver nanoparticles from H. undatus fruit peel and their therapeutic applications

The green synthesis of nanoparticles (NPs) gained significant impacts in various fields due to the use of eco-friendly approaches. In this study, silver nanoparticles (AgNPs) were synthesized from the aqueous extract of Hylocereus undatus fruit peel. The presence of AgNPs was analysed using characterization methods such as UV‒Vis, FTIR, GCMS, XRD, EDAX, and FESEM. The synthesized AgNPs showed greater antibacterial activity against Escherichia coli than against Streptococcus pneumoniae. The antifungal activity against Candida albicans was greater than that against Candida tropicalis. The IC50 value for the antibiofilm activity of the AgNPs was 2.81 µg/mL, whereas that of the H. undatus peel extract was 1.34 µg/mL. The invitro antioxidant activity of the AgNPs was evaluated using two different methods. The DPPH radical scavenging activity of the AgNPs and fruit peel extract was observed with IC50 values of 3.8 and 2.03 µg/mL respectively. On the other hand, nitric oxide radical scavenging activities were recorded and the IC50 values were calculated to be 2.8 and 2.3 µg/mL. The AgNPs demonstrated thrombolytic activity in human blood with 10, 32.36, and 56.25% lysis. The cytotoxicity of the AgNPs was minimal, with an IC50 of 0.2 µg/mL and the peel extract had the greatest cytotoxicity with an IC50 of 0.3 µg/mL. The findings of this study demonstrated that the synthesized AgNPs from H. undatus peel extract could be potential candidates for treating prostate cancer.Graphical abstract

Universal CAR T cells targeted to HER2 with a biotin-trastuzumab soluble linker penetrate spheroids and large tumor xenografts that are inherently resistant to trastuzumab mediated ADCC.

CAR T cell therapies face challenges in combating solid tumors due to their single-target approach, which becomes ineffective if the targeted antigen is absent or lost. Universal CAR T cells (UniCAR Ts) provide a promising solution by utilizing molecular tags (linkers), such as biotin conjugated to monoclonal antibodies, enabling them to target a variety of tumor antigens. Recently, we showed that conventional CAR T cells could penetrate the extracellular matrix (ECM) of ADCC-resistant tumors, which forms a barrier to therapeutic antibodies. This finding led us to investigate whether UniCAR T cells, targeted by soluble antibody-derived linkers, could similarly tackle ADCC-resistant tumors where ECM restricts antibody penetration. We engineered UniCAR T cells by incorporating a biotin-binding monomeric streptavidin 2 (mSA2) domain for targeting HER2 via biotinylated trastuzumab (BT). The activation and cytotoxicity of UniCAR T cells in the presence or absence of BT were evaluated in conventional immunoassays. A 3D spheroid coculture was set up to test the capability of UniCAR Ts to access ECM-masked HER2+ cells. For in vivo analysis, we utilized a HER2+ xenograft model in which intravenously administered UniCAR T cells were supplemented with intraperitoneal BT treatments. In vitro, BT-guided UniCAR T cells showed effective activation and distinct anti-tumor response. Upon target recognition, IFNγ secretion correlated with BT concentration. In the presence of BT, UniCAR T cells effectively penetrated HER2+ spheroids and induced cell death in their core regions. In vivo, upon intravenous administration of UniCAR Ts, circulating BT linkers immediately engaged the mSA2 domain and directed effector cells to the HER2+ tumors. However, these co-treated mice died early, possibly due to the lung infiltration of UniCAR T cells that could recognize both native biotin and HER2. Our results suggest that UniCAR T cells guided with soluble linkers present a viable alternative to conventional CAR T cells, especially for patients resistant to antibody therapy and those with solid tumors exhibiting high antigenic variability. Critical to their success, however, is the choice of an appropriate binding domain for the CAR and the corresponding soluble linker, ensuring both efficacy and safety in therapeutic applications.

Transdermal Administration of Nanobody Molecules using Hydrogel‐Forming Microarray Patch Technology: A Unique Delivery Approach

AbstractNanobody molecules, derived from heavy‐chain only antibodies in camelids, represent the next generation of biotherapeutics. In addition to low immunogenicity, high stability, and potency, their single‐domain format facilitates the construction of multivalent molecules for therapeutic applications. Although predominantly administered using a hypodermic syringe and needle, alternative delivery methods are under investigation. That said, the transdermal route has yet to be explored. Therefore, microarray patch (MAP) technology, offering a potentially high dose, pain‐free transdermal system, is employed in this study. Trivalent Nanobody molecules, with and without half‐life extension (VHH and VHH[HLE]), are formulated into hydrogel‐forming MAPs, with pharmacokinetic parameters assessed in Sprague–Dawley rats. VHH MAPs exhibited a sustained release profile, with a serum concentration of 19 ± 9 ng mL−1 24 h post‐administration. In contrast, a subcutaneous (SC) injection showed faster clearance, with a serum concentration of 1.1 ± 0.4 ng mL−1 at 24 h. For VHH(HLE), both SC and MAP cohorts achieved a maximum serum concentration (Tmax) at 24 h. The MAP cohort displayed a notable increase in VHH(HLE) serum levels between 6–24 h, dropping after MAP removal. This study has exemplified MAPs potential for delivering advanced biologics, indicating the transdermal route's promise for pain‐free, patient‐friendly administration of Nanobody molecules.

Updates in pelvic neuromodulation: the role of pelvic neuromodulation in pelvic disorders

Pelvic disorders affecting both male and female patients are major areas of concern for clinicians in cases where pharmacotherapy and behavioral therapy are not effective. In such cases, pelvic neuromodulation has become an alternative therapy that could relieve chronic pelvic pain and enhance the quality of life. The goal of this paper was to present a summary of the current therapeutic applications of various pelvic neuromodulation techniques and their efficacy in treating patients with a range of pelvic illnesses. Based on the available literature, this review assessed the validity and significance of the last 10 years’ advancements in the fields of sacral neuromodulation (SNM), posterior tibial nerve stimulation (PTNS), and pudendal neuromodulation (PNM), including meta-analyses, randomized controlled trials, and observational, prospective, and retrospective studies.