Therapy Research Articles

Hemorrhoid (Pile) and its Treatment with Botanicals: An Overview

: Hemorrhoid disease is a common condition that can have a significant impact on an individual's quality of life due to its associated symptoms. A wide range of management options are available for the treatment of hemorrhoid disease, including various yogic kriyas, herbal remedies, flavonoids, tocotrienols, topical treatments, hydrotherapy, dietary approaches, and surgical procedures. This review aims to focus specifically on the use of botanicals for the treatment of hemorrhoid disease, covering various aspects of its treatment.

Advances in the Development of Non-Structural Protein 1 (NsP1) Inhibitors for the Treatment of Chikungunya Virus Infection.

Chikungunya is a re-emerging viral infection of worldwide concern, and new antiviral therapeutics are necessary to combat this disease. Inhibitors of the non-structural protein 1 (NsP1), which shows Methyltransferase (MTase) activity and plays a crucial in the Chikungunya virus (ChikV) replication, are exhibiting promising results. This review aimed to describe recent advances in the development of NsP1 inhibitors for the treatment of ChikV disease. High-throughput screening of novel ChikV NsP1 inhibitors has been widely performed for the identification of new molecule hits through fluorescence polarization, Western blotting, ELISA-based assay, and capillary electrophoresis assays. Additionally, cell-based assays confirmed that the inhibition of ChikV NsP1 abolishes viral replication. In summary, pyrimidine and pyrimidin-7(6H)-one derivatives, GTP and nucleoside analogs have been demonstrated to show inhibitory activity and are considered promising scaffolds that provide useful knowledge for the research and development of new NsP1 inhibitors as potential treatment of Chikungunya re-emerging disease. </p>.

Access to Care and Health-Related Quality of Life in Multiple Sclerosis.

Despite their high health care use, it is unclear whether the health care needs of people with MS are being met and what their priorities are. We assessed priorities for access to, and affordability of care, by people living with MS in the United States. We also tested the association between perceived inadequate access to care and health-related quality of life (HRQoL). In Fall 2022, we conducted a cross-sectional survey of participants in the North American Research Committee on Multiple Sclerosis Registry about access to care and HRQoL (Health Utilities Index Mark III). We used multivariable polytomous logistic regression to test sociodemographic and clinical factors associated with access to care. We used multivariable linear regression analysis to test the association between access to care and HRQoL. We included 4,914 respondents in the analysis, of whom 3,974 (80.9%) were women, with a mean (SD) age 64.4 (9.9) years. The providers who were most reported as needed but inaccessible were complementary providers (35.5%), followed by allied health providers (24.2%), occupational therapists (22.7%), and mental health providers (20.7%). Over 80% of participants reported that it was important or very important to be able to get an appointment with their primary MS health care provider when needed, to have sufficient time in their appointments to explain their concerns, to see their neurologist if their status changed, and that their health care providers communicated to coordinate their care. Participants who reported needing to see the provider but not having access or seeing the provider but would like to see them more often had lower HRQOL (ranging from -0.059 to -0.176) than participants who saw the provider as much as needed. Gaps in access to care persist for people with MS in the United States and substantially affect HRQoL. Improving access to care for people with MS should be a health system priority.

Akkermansia muciniphila: A promising probiotic against inflammation and metabolic disorders.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy.

In the field of precision and personalized medicine, the next generation sequencing method has begun to take an active place as genome-wide screening applications in the diagnosis and treatment of diseases. Studies based on the determination of the therapeutic efficacy of personalized drug use in cancer treatment in the size of the transcriptome and its extension, lncRNA, have been increasing rapidly in recent years. Targeting and/or regulating noncoding RNAs (ncRNAs) consisting of long noncoding RNAs (lncRNAs) are promising strategies for cancer treatment. Within the scope of rapidly increasing studies in recent years, it has been shown that many natural agents obtained from biological organisms can potentially alter the expression of many lncRNAs associated with oncogenic functions. Natural agents include effective small molecules that provide anti-cancer effects and have been used as chemotherapy drugs or in combination with standard anti-cancer drugs used in routine treatment. In this review, it was aimed to provide detailed information about the potential of natural agents to regulate and/or target non-coding RNAs and their mechanisms of action to provide an approach for cancer therapy. The discovery of novel anti-cancer targets and subsequent development of effective drugs or combination strategies that are still needed for most cancers will be promising for cancer treatment.

Efficacy of the combination of tadalafil and tamsulosin versus tadalafil alone as a medical expulsive therapy for stone L1/3 ureter 10 mm or less: A prospective comparative placebo-controlled study

Abstract Background The lifetime occurrence of urinary stones is approximately 1%–15%, and the peak age of occurrence is 30 years. Approximately one fifths of urinary tract stones are found in the ureter, of which two thirds are in the distal ureter. Many drugs, including phosphodiesterase-5 inhibitors (PDE5Is) and α-blockers, are used to relax the smooth muscles in medical expulsive therapy (MET). We aimed to compare the combination of tadalafil and tamsulosin versus tadalafil alone as MET for stones in the L1/3 ureter of 10 mm or less. Materials and methods A total of 150 patients with L1/3 ureteric stones measuring 10 mm or less were enrolled in the study and randomly assigned to one of 3 equal groups using a computer-generated random number. Patients in group A prescribed tadalafil 10 mg/d. However, those in group B were prescribed tamsulosin 0.4 mg and tadalafil 10 mg/d, whereas those in group C received a placebo once daily. Stone expulsion rate and pain recurrence were evaluated after 14 days. Results The stone expulsion rate was significantly higher in the tadalafil and tamsulosin groups and the tamsulosin group than in the placebo group in the current study by 68% in the combination group, 64% in the tadalafil alone group, and 42% in the placebo group (p = 0.019). In the current study, a combination was associated with lower pain recurrence than tadalafil alone or placebo, with means of 1.06, 1.9, 2.98 (with a p value of 0.001). Stone size was not effective in any group. Conclusions The combination of PDE5Is and α-blockers effectively increases the expulsion of lower ureteric stones (5–10 mm), but with the same effect as PDE5Is alone, with the advantage of decreasing pain recurrence. Stone size did not affect the expulsion rate in patients who received MET for stones less than 1 cm in size.

Management of primary sclerosing cholangitis: Current state-of-the-art

Primary sclerosing cholangitis is a chronic liver disease characterized by progressive inflammation and fibrosis of medium-large bile ducts, most commonly in association with inflammatory bowel disease. Most patients have a progressive disease course, alongside a heightened risk of hepatobiliary and colorectal cancer. Medical therapies are lacking, and this, in part, reflects a poor grasp of disease biology. As a result, current management is largely supportive, with liver transplantation an effective life-prolonging intervention when needed, but not one that cures disease. Emerging therapies targeting disease progression, as well as symptoms such as pruritus, continue to be explored. The trial design is increasingly cognizant of the application of thoughtful inclusion criteria, as well as better endpoints aimed at using surrogates of disease that can identify treatment benefits early. This is hoped to facilitate much-needed advances toward developing safe and effective interventions for patients.

Serious games are more than just games.

Serious games (SG) or educational games are complete games designed for a specific purpose that fulfill both their classic function of entertainment and promote the learning of specific concepts or skills and optimize health care in general. In the pediatric setting, these games combine strategies to educate about health issues, promote healthy behaviors, provide therapy or medical treatment. SG have been shown to promote adherence to treatment in children with chronic diseases, reduce anxiety in those undergoing invasive medical procedures, and stimulate the development of cognitive, emotional, or psychomotor skills. However, it is important to emphasize that the success of SG in pediatrics depends to a large extent on game quality, their design based on clear objectives, and their accurate adaptation to the individual needs and preferences of patients.

Herbal Remedies: An Emerging Alternative for the Treatment of Pandemic Diseases

Abstract: Pandemics are large-scale epidemics of infectious illness that may cause major economical, cultural, and political upheaval while also increasing illness and mortality across a huge geographic area. Evidence shows that pandemics have increased during the last century as a result of increasing international travel and connectivity, industrialization, agricultural expansion, and higher destruction of the natural environment. Over time, emerging pathogen strains cause pandemics that raise suffering, death, and instability in countries. Flu, plague, cholera, HIV, and the current COVID-19 pandemic caused by a novel coronavirus are just a few of the pathogen outbreaks. Unfortunately, given the lack of information and instruments to tackle the problem, managing new and developing infections is frequently challenging. Yet, the use of herbal remedies to treat new and developing infectious illnesses has received much interest. Until the invention of antibiotics, herbal plants, their preparations, and extracted phytoconstituents were reported to be efficient in reducing infectious diseases. Plants contain numerous complex metabolites, such as amino acids, alkaloids, tannins, flavonoids, terpenoids, and glycosides, that show different therapeutic activities. This review provides vital and useful information regarding herbal drugs and their effectiveness against various pathogens that cause major pandemics.

Acupuncture in the Treatment of Male Infertility: A Review

In recent years, there has been a global decline in the quality of human semen, leading to a gradual increase in the incidence of infertility, which significantly impacts men’s health. Due to the complex etiology of male infertility, clinical treatment is predominantly confined to drugs, surgery, and assisted reproductive technology. However, the efficacy of these approaches often falls short of meeting clinical needs, prompting the exploration of new treatment methods. Acupuncture, a crucial component of traditional Chinese medicine (TCM), has gained increasing prominence in the treatment of male infertility, yielding noteworthy results. This article offers an overview of TCM’s perspective on male infertility, explores the clinical efficacy of acupuncture in treating male infertility and the corresponding mechanisms, and summarizes the existing challenges in the current acupuncture-based treatment of male infertility. It also clarifies the validity of acupuncture and provides references for the future development of acupuncture in the treatment of male infertility.

Bacoside A: A Promising Medication for Treatment of Various Disorders

Abstract: Bacoside A is a triterpenoid saponin and nootropic herb that can be extracted from Bacopa monnieri Linn., Scrophulariaceae. It is a glabrous and succulent herb used traditionally for centuries in treating various illnesses, mainly as a cardiotonic and nerve tonic, and has been considered an eminent Ayurvedic medicine. Various studies reported that the herb consists of a wide range of potentially bioactive, phytochemical constituents with synergistic effects. Bacoside A is a major constituent of B. monnieri, with diverse biological functions and significant therapeutic potential, as given by various researchers and preclinical studies. It possesses various biological activities such as hepatoprotective, anti-osteoporotic, anti-ulcerogenic, anti-inflammatory, anti-tumor, wound healing, and neuroprotective effects. This review compiled the preclinical evidence-based studies and present knowledge of bacoside A's potential benefits and fruitful impact on human health, and we provided a comprehensive perspective of bacoside A in various disease treatments.

A novel near-infrared fluorescent probe for butyrylcholinesterase: Research for screening of natural anti-AD inhibitors

Elevated levels of butyrylcholinesterase (BuChE) have the potential to be predictive in the timely detection and diagnosis of Alzheimer's disease (AD). By inhibiting of BuChE activity can raise acetylcholine levels and intervene AD processes. Therefore, BuChE as an important factor in treatment AD has been given more and more attention in clinical studies. Given the facts above, in this study, for precise monitoring of BuChE level changes and screening for possible butyrylcholinesterase inhibitor (BuChEI) for AD diagnosis and therapy, a near-infrared (NIR) fluorescence probe (NFP-BuChE) was created. The probe exhibits excellent sensitivity and selectivity for BuChE. NFP-BuChE has been successfully applied to the detection of endogenous BuChE levels in live cells, and we successfully constructed a screening system for BuChEI on cells and a novel natural efficient BuChEI (matrine) was discovered and identified, which significantly reduced BuChE activity and thus alleviated AD symptoms. Most importantly, for the first time, we measured the changes of BuChE levels in zebrafish (0-4 days) after fertilization, various organs of zebrafish, and AD zebrafish modeled by different concentrations of AlCl3 by NFP-BuChE, and at the same time, we also validated the inhibitory effect of matrine on BuChE by NFP-BuChE in zebrafish. In addition, NFP-BuChE has also been successfully used to measure the changes of BuChE levels in the brains of AD mice. These findings imply that NFP-BuChE is a potentially useful molecular tool for screening possible natural BuChEI quickly and for monitoring changes in BuChE activity, and it is expected that more value will be explored in mice. In addition, matrine and its derivatives are promising options for future Alzheimer's disease treatments.

Autoencoder-based drug synergy framework for malignant diseases

Drug combination emerges as a viable option for the treatment of malignant diseases. Drug combination outperforms monotherapy by improving therapeutic efficacy, reducing toxicity, and overcoming drug resistance. To find viable drug combinations it is difficult to traverse empirically because of enormous combinational space. Machine learning and deep learning approaches are used to uncover novel synergistic drug combinations in enormous combinational space. Here, AESyn, a novel autoencoder-based drug synergy framework for malignant diseases using a bag of words encoding is proposed. The bag of word encoding technique is used to extract drug-targeted genes. The framework utilized screening data from NCI-ALMANAC, and O’Neil datasets. Autoencoders take drug embeddings with drug-targeted genes as input for processing. The autoencoder in the proposed framework is used to extract drug features. The proposed framework is evaluated on classification and regression metrics. The performance of the proposed framework is compared with existing methods of drug synergy. According to the findings, the proposed framework achieved high performance with an accuracy of 95%, AUROC of 94.2%, and MAPE of 7.2. The autoencoder-based framework for malignant diseases using an encoding technique provides a stable, order-independent drug synergy prediction.

The Role of Ocimene in Decreasing α-Synuclein Aggregation using Rotenone-induced Rat Model.

Parkinson's disease is defined by the loss of dopaminergic neurons in the midbrain of substantia nigra associated with Lewy bodies. The precise mechanism is not yet entirely understood. The study aims to determine whether ocimene has antiparkinsonian activity by reducing α-Synuclein aggregation levels in the brains of rotenone-induced rat models. 36 male rats were used for six groups, with six animals in each group. Vehicle, control (rotenone, 2.5 mg/kg, i.p), standard (L-Dopa, 10 mg/kg, i.p), Test drug of low dose (66.66 mg/kg, i.p), medium dose (100 mg/kg, i.p), and high dose (200 mg/kg, i.p) were administered to the rats. The open field, actophotometer, hanging wire, and catalepsy tests were used to assess the rat's motor performance. The expressions of biomarkers such as AchE, D2 Receptor, and α- Synuclein were evaluated, and their level of expression in the brain samples was checked using ELISA. Histopathological analysis was also carried out to determine the degree of neuron degeneration in the brain samples. The open field test showed significant anxiety levels, whereas test groups showed fewer anxiety levels but increased motor activity. The biochemical tests revealed that rotenonetreated rats had higher levels of AchE, but ocimene-treated rats had a significant decrease in AchE levels. The test drug-treated rats also expressed high levels of D2 receptors. In ocimenetreated rats, α-Synuclein aggregation was reduced, however, in rotenone-treated rats' brain samples, higher clumps of α-Synuclein were observed. Ocimene has neuroprotective properties. As a result, this essential oil might be helpful as a therapeutic treatment for Parkinson's disease.

Fluorinated dendrimer-mediated miR-30a delivery regulates the inflammation of macrophages and mitigates the symptoms of rheumatoid arthritis

Abnormal expression of microRNAs (miRNAs) plays a significant role in the pathogenesis of rheumatoid arthritis (RA), and thus miRNA-based therapy has emerged as a promising approach for the RA treatment. Herein, miR-30a was successfully screened and identified to be an essential mediator for the inflammation of RA. MiR-30a could directly target the Snai1 gene and further regulate the Cad11 expression to inhibit the NF-κB and MAPK signaling pathways, contributing to the anti-inflammatory effect. To enhance the therapeutic outcome of miR-30a, fluorinated polyamidoamine dendrimer (FP) was developed as the carrier to achieve the miR-30a delivery in the mice of collagen-induced arthritis. The carrier FP and miR-30a formed stable nanocomplexes and effectively mediated the transfection of miR-30a to execute the anti-inflammatory response in lipopolysaccharide-stimulated macrophages. Further, the intravenous administration of FP/miR-30a showed obvious accumulation in the inflamed joints and inhibited the inflammatory response via the Snai1/Cad11 axis, thereby contributing to the anti-arthritic efficacy. In addition, the FP/miR-30a nanocomplexes displayed favorable biocompatibility, as they did not cause the damage of organs following the systemic administration. Taken together, our study demonstrated that miR-30a is an effective anti-inflammatory oligonucleotide and the fluorinated dendrimer-mediated miR-30a delivery possesses the potential to be a promising approach for the treatment of RA and other autoimmune diseases.

Safety and efficacy of vacuum-assisted mini-percutaneous nephrolithotomy for the treatment of renal stone disease: an analysis of stone free status and postoperative infectious complications.

Vacuum-assisted mini-percutaneous nephrolithotomy (vmPCNL) is being increasingly adopted due to its faster operating times and lower incidence of postoperative infectious complications (IC), however, studies have been limited by small sample sizes. We hypothesize that vmPCNL is an efficacious treatment for renal stone disease with acceptable stone-free rates (SFR) and low incidence of IC. The objectives of this study were to measure SFR three months after surgery, determine the factors influencing SFR, and determine the rates of postoperative IC after vmPCNL. Seven hundred and sixty seven patients underwent vmPCNL for the treatment of renal stones > 20 mm at a single institution. Patients underwent postoperative computed tomography at three months to assess SFR. Postoperative fever and SIRS/Sepsis were recorded for individual patients. Multivariate logistics regression was performed to assess predictors of SFR. The SFR was found to be 73.7% at three months. Stone burden (OR 0.39, 95% CI [0.33-0.46]) and age (OR 1.03, 95% CI [1.01-1.04]) emerged as statistically significant predictors of SFR on multivariate analysis. 5.5% of patients experienced postoperative fever, while 2.9% experienced SIRS/Sepsis. This is the largest continuous cohort of patients to undergo vmPCNL for stone disease and demonstrates that vmPCNL is safe and efficacious, with an SFR of 74% at three months. The incidence of postoperative fever and SIRS/Sepsis is 5.5% and 2.9% respectively. Further randomized studies with large sample sizes are required to ascertain the rates of these complications in comparison to conventional approaches.

Choroidal melanocyte secretome from cultured cells and tissue-engineered choroid models exposed to acute or chronic oxidative stress

The choroid, located between the retina and the sclera, is a vascularized and pigmented connective tissue, playing a crucial role in providing oxygen and nutrients to the outer layers of the retina, and in absorbing excessive light. How choroidal melanocytes (CMs) participate in tissue homeostasis through paracrine signaling with neighboring cells is poorly understood. In this study, using two-dimensional and three-dimensional models, we aimed to identify proteins secreted by CMs under different oxidative stress conditions. To do so, CMs, choroidal fibroblasts (CFs), and retinal pigment epithelial (RPE) cells were isolated from native human RPE/choroidal tissues and expanded. RNA was isolated and processed for gene profiling analysis. The self-assembly approach of tissue engineering was used to form 3D stromal substitutes, and RPE cells and/or CMs were added to produce 3D models with different cell combinations. The medium conditioned by cells in 2D and 3D cultures was collected in a non-stressed condition and following acute or chronic oxidative stress exposures, then proteome and ELISA analyses were performed to identify cytokines secreted majorly by CMs. RNA analysis revealed 15 secretome-related transcripts that were more abundantly expressed in CMs compared to the other 2 cell types, including serpin family F member 1 (SERPINF1) (coding for pigment epithelium-derived factor; PEDF) and secreted phosphoprotein 1 (SPP1) (coding for osteopontin). At the protein level, the expression of osteopontin and PEDF was higher in CMs of different age groups compared to CFs and RPE cells. In the 3D models containing CMs, cytokine arrays also identified macrophage inflammatory protein (MIP)-1α/MIP-1β in non-stressed, MIP-1α/MIP-1β, interleukin (IL)-24, and angiogenin following an acute oxidative stress, and macrophage migration inhibitory factor (MIF), granulocyte-colony stimulating factor (G-CSF), intercellular adhesion molecule-1 (ICAM-1), and IL-1α following a chronic oxidative stress. This study identifies for the first time trophic factors secreted by CMs that could influence neighboring cells through paracrine signaling. Of those, PEDF and osteopontin are antioxidative proteins that are known to attenuate oxidative stress damage. Identifying factors that can help manage oxidative stress in the posterior segment of the eye may lead to promising treatments for retinal diseases.

Polygonatum sibiricum polysaccharides: A promising strategy in the treatment of neurodegenerative disease.

Neurodegenerative diseases (NDDs), as a neurological disorder characterised by neuronal degeneration and death, are a serious threat to human health and have long attracted attention due to their complex pathogenesis and the ineffectiveness of therapeutic drugs. Existing studies have shown that Polygonatum Sibiricum polysaccharides (PSP) have immunoregulatory, antioxidant, anti-inflammatory and other pharmacological effects, and their neuroprotective effects have been demonstrated in several scientific studies. This paper reviews the main pharmacological effects and mechanisms of PSP in the protection and treatment of NDDs, to provide a reference for the clinical application and basic research of PSP in NDDs.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Recent Advances in Pyrazole-based Protein Kinase Inhibitors as Emerging Therapeutic Targets.

Pyrazole-scaffold protein kinase inhibitors (PKIs) have emerged as promising therapeutic agents for the treatment of various diseases, such as cancer, inflammatory disorders, and neurological diseases. This review article provides an overview of the pharmacological properties of pyrazole-scaffold PKIs, including their mechanism of action, selectivity, potency, and toxicity. The article also summarizes the recent developments in the design and synthesis of pyrazole-scaffold PKIs, highlighting the structural features and modifications that contribute to their pharmacological activity. In addition, the article discusses the preclinical and clinical studies of pyrazole-scaffold PKIs, including their efficacy, safety, and pharmacokinetic properties. A comprehensive search has been conducted on several online patent databases, including the United States Patent and Trademark Office (USPTO), the European Patent Office (EPO), and the World Intellectual Property Organization (WIPO). The search was conducted using pyrazole as the keyword. The search was limited to patents filed between 2015 and 2022. Patents were included if they involved articles in the fields of protein kinase inhibitors, and included literature on some pyrazoles and their pharmacological activities. Data were extracted from each included patent on the following variables: patent title, patent number, inventors, assignee, filing date, publication date, patent type, and field of invention. Data were extracted from each patent using a standardized form to ensure consistency and accuracy. The design and pharmacological evaluation of organic compounds containing pyrazole structure as biologically active substances have been done, and the key structures from the pharmacological data obtained as protein kinase inhibitors have been addressed in detail. The review concludes with a discussion on the current challenges and future directions for the development of pyrazole-scaffold PKIs as therapeutic agents. Overall, this review article provides a comprehensive summary of the pharmacological properties of pyrazole-scaffold PKIs, which will be of interest to researchers and clinicians in the field of drug discovery and development.