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Diabetes is one of the most common chronic ailments; its incidence has reached epidemic proportions in the 21st century. Diabetes significantly increases micro and macrovascular complications, which are effectively managed with statins. Therefore, statins' pharmacokinetics, pharmacodynamics, and pharmacogenetics have been extensively studied. Although statins act as a keystone in preventing cardiovascular complications, at the same time, they pose a threat to the quality of life of diabetics due to the resulting muscular side effects. This article summarizes the prevalence, clinical manifestations, pathophysiology, and risk factors of statin-induced myopathy in diabetic patients. Among the diverse predisposing risk factors, the primary variables identified for causing myopathy in diabetic patients include age, gender, ethnicity, duration and severity of illness, comorbid conditions, level of physical activity, alcohol use, cholecalciferol (vitamin D3) levels, type and dose of statins, and anti-diabetic drugs or other drugs used concomitantly. In addition, cardiovascular risk quotients also potentially impact diabetic patients making them more vulnerable to developing myopathy from statins. Therefore, this study highlights the importance of managing statin-associated myopathic side effects by providing consensus guidelines on diagnostic, monitoring, and treatment strategies. We also discussed statins' prognostic value in reducing cardiovascular events in diabetic individuals.
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Chronic obstructive pulmonary disease (COPD) constitutes a set of heterogeneous symptoms affecting millions of people worldwide. The associated comorbidities developing in COPD involve dysregulation in physiological pathways resulting from systemic inflammation in respiratory airways. In addition to mentioning the pathophysiology, stages, and consequences of COPD, this paper also defines red blood cell (RBC) indices such as hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cell distribution width, and RBC count. It explains the role of RBC indices and RBC structural abnormalities with disease severity and exacerbations in COPD patients. Although many factors have been studied as a marker of morbidity and mortality for COPD patients, RBC indices have emerged as revolutionary evidence. Therefore, the effectiveness of evaluating RBC indices in COPD patients and their importance as a negative predictor of survival, mortality, and clinical outcomes have been debated through rigorous literature reviews. Furthermore, the prevalence, mechanisms of development, and prognosis of underlying anemia and polycythemia in COPD have also been evaluated, with anemia most significantly associated with COPD. Therefore, more studies should be conducted to address underlying anemia in COPD patients to lessen the severity and disease burden. Correcting the RBC indices in COPD patients remarkably impacts the quality of life and reduces in-patient admissions, healthcare resource utilization, and costs. Hence, it is noteworthy to understand the significance of considering RBC indices while dealing with COPD patients.
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Diabetes mellitus (DM) is a major cause of morbidity worldwide. The prevalence of DM has doubled over the last 35 years and is escalating. Various complications and manifestations of diabetes have caused numerous deaths worldwide, with numbers increasing every year. There have been many advances and breakthroughs over the past decade in the management of DM. The major focus of many research studies has been to evaluate effective medication combinations, preventative measures, and the way to control such morbid conditions. Our focus in this review is to discuss specific secondary prevention techniques with the diabetes log sheet and educational literature on its effectiveness in controlling diabetes. Hemoglobin A1c (HbA1c) has been accepted as a diabetes control measure in many resources worldwide. Here, we have assessed articles on the effectiveness of the diabetes log sheet and educational literature on HbA1c levels. We will begin with a few key points to acknowledge diabetes initially, followed by discussing the effectiveness of the diabetes log sheet and literature on HbA1c.
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Gastric carcinoma is the third leading cause of cancer mortality worldwide. In 2018, the incidence of gastric carcinoma worldwide was over 1,000,000 new cases, with approximately 783,000 deaths. The rate of new cases is noticeably increased in Eastern Asia. Helicobacter pylori is responsible for the increased incidence of gastric cancer. In the year 2015, H. pylori had an approximate prevalence of 4.4 billion positive cases worldwide, with the most positive cases found within the region of Africa, Latin America and the Caribbean, and of Asia. H. pylori is known to have multiple strains which allow it to survive in the host cell epithelium chronically. Research has shown many factors which play a significant role in developing infection and thereafter its progression to gastric carcinoma. After H. pylori colonizes the gastric mucosa, its effects can be potentiated by virulence factors, host factors, and environmental factors. H. pylori contains virulence factors that aid in the adhesion, translocation, inflammation, and infectivity of the host gastric epithelium. It alters the functions of the host immune response and cytokines, utilizing these factors to invade and persist in the gastric epithelium for a long period of time. The human body will identify H. pylori to be foreign and will exacerbate an inflammatory response in an effort to eradicate the bacterium. Consequently, this will cause H. pylori to induce a serious infection which may progress to cancer. In this review, we will discuss the various factors involved in the infectious process of H. pylori and how they help the infection progress to gastric carcinoma. This will allow us to better understand and modulate treatments to effectively eradicate this bacterium before it triggers the body into developing cancer.
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In 2020, the incidence of leukemia was 474,519 with 311,594 mortality worldwide. In 2021, the American Cancer Society (ACS) has estimated 61,090 new cases of leukemia to occur within the United States. It has also been reported that the most common cause of death in children from one to fourteen years old is oncological, with leukemia being the most frequent cause. A phenomenon known as the Warburg effect has been affiliated with cancer. The Warburg effect is a metabolic abnormality of lactic acidosis in malignancies, with most cases presenting as hematological malignancies such as leukemia. Although many theories have been formulated to clarify the role of the Warburg effect, the exact role still remains uncertain. Four suggested theories on why the Warburg effect happens to include cell signaling, adenosine triphosphate (ATP) synthesis, biosynthesis, and the tumor microenvironment. The Warburg effect occurs in leukemia with the help of enzymes such as pyruvate kinases M2 (PKM2), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), and fibroblast growth factor receptor 1 (FGFR1). In this literature, we explain the proposed hypotheses of the Warburg effect, along with the molecular mechanism of how leukemia is able to produce lactic acid, with the intent to better understand this phenomenon.
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Epilepsy is a disorder that causes unprovoked seizures regularly. It affects between 1% and 3% of the population. After the first seizure, the chances of having another one are almost 40%-52%. The etiology of febrile seizures in children with sickle cell disease is still unknown. In some groups, iron deficiency anemia has been linked to an increased risk of seizures. Although the reason and process are uncertain, some people believe that taking iron supplements can help prevent seizures. This literature covers haptene, non-haptene immune-related hemolysis, and oxidative processes activated by anti-seizure medications (ASMs). In epileptic patients, ASMs can cause anemia. Folic acid can be given to carbamazepine-treated anemic patients. There is growing evidence that it improves hemoglobin and leukocytes in individuals who take it. Therefore, one of the most efficient strategies to avoid future seizures is to take ASMs daily to maintain an even level of anticonvulsant in the body. To prevent further seizures, lifestyle changes are essential. Further studies and clinical trials are warranted to prove a clear association between epilepsy and hematologic disease, which will improve quality of life in the future.
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Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. After the introduction of chimeric antigen receptor (CAR) T cell therapy, promising results have been evidenced. In this therapy, T cells are derived from the patient and modified in-vitro to induce receptors that later target specific antigens when they are injected into patients. CAR T cells use three mechanisms to kill tumor cells: cytolytic pathways, cytokine release, and Fas/FasL axis. In this review, we highlight the different tumor markers targeted for therapy against multiple myeloma (MM). Target antigens for CAR T cell therapy include B-cell maturation antigen (BCMA), signaling lymphocyte activation molecule F7 (SLAMF7), CD38, CD138, CD19, immunoglobulin kappa light chain, orphan G protein-coupled receptor class C group 5 member D (GPRC5D). With the benefit of improving survival and prognosis, this therapy does carry a risk of some adverse events such as cytokine release syndrome, encephalopathy, infections, hypogammaglobulinemia, and tumor lysis syndrome.
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A strong association is noted between depression and early perimenopause as well as menopause. The association was found to be the greatest in women with natural menopause at the age less than 40 years. Excessive corticotropin-releasing hormone (CRH) levels in depression lead to inhibition of the hypothalamic-pituitary-gonadal (HPG) axis and increased cortisol levels which further inhibits the action of gonadotropin-releasing hormone (GnRH) neurons, gonadotrophs, and gonads. The resulting changes in luteinizing hormone (LH) amplitude, follicle-stimulating hormone (FSH) levels, and LH pulse frequency were noted in patients with depression. Besides depression, earlier surgical menopause is associated with cognitive decline. In addition, it is seen that menopausal changes predisposed females to an increased risk of depression. The association between dysmenorrhea and depression was found to be bidirectional and congruent in most studies. Patients with dysmenorrhea and coexisting depression had enhanced pain perception along with a poor response to pain relief measures. Even the treatment of underlying depression has been shown to cause menorrhagia. On the other hand, amenorrhea has also been reported as a side effect of sertraline and electroconvulsive therapy. Menstrual disorders contribute to a significant number of outpatient gynecological visits per year in the United States. Co-existing or history of depression can either be the cause of or interfere in the treatment of these disorders. Furthermore, the treatment of depression can be the etiology of various menstrual abnormalities, while menstrual disorders themselves could be the cause of depression. The increasing prevalence of depression, women's health, multiple female-specific subtypes, and the preexisting burden of menstrual disorders necessitates more detailed studies on the effects of depression on the menstrual cycle.
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Factor V Leiden (FVL) G1619A mutation and prothrombin gene (PTG) G20210A are the most common inherited thrombophilias. They have been associated with various obstetric complications such as venous thromboembolism, recurrent pregnancy loss, preeclampsia, abruptio placentae, and small for gestational age fetus. The prevalence of these two mutations is 3-15% in Caucasians and is assumed to be far less common in other ethnic populations. However, there have been several controversies regarding advising routine screening of these thrombophilias because of a widely variable strength of association between different ethnic groups, as well as contradictory conclusions by different studies in regards to the association. In this study, the literature was analyzed thoroughly for the effect of FVL G1619A and PTG G20210A mutations on various obstetric outcomes. A review of multiple case-control and prospective studies suggests that despite the availability of robust data on this subject the results remain inconclusive and insubstantial. Further superior quality research, preferably prospective studies, is warranted to conclusively establish this relationship and to enable practitioners to follow a definitive protocol in the screening of various populations for these mutations to achieve an improved pregnancy outcome.
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Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting adults. CLL results due to uncontrolled accumulation of B lymphocytes in the body with the clinical spectrum ranging from comparatively benign disease to an aggressive form. The disease pathogenesis lies in molecular genetics, the most common alteration being the deletion in the long arm of chromosome 13, at position 14 (13q14) region. This deletion leads to the loss of important microRNAs which are involved in maintaining the critical balance of the apoptosis mechanism of cell death of B lymphocytes. As such, the imbalance contributes towards B cells' immortality and, thus, CLL arises. This significant 13q14 deletion contributes to CLL's pathogenesis and paves the way for CLL treatment, hence affecting the prognosis of the affected patients. Furthermore, the size of deletion of the long arm of chromosome 13 (13q) has a remarkable effect on its prognosis and therapeutic intervention. The minimal deleted region (MDR)/small deletion or long 13q loss/mutation, and biallelic 13q deletion or monoallelic 13q deletion are commonly seen. 13q14 deletion is an initiating defect targeting tumor suppressor gene locus deleted in lymphocytic leukemia 2 (DLEU2))/microRNA15A (MIR15A)/microRNA 16-1 (MIR 16-1). Regarding CLL treatment, conventional therapy with alkylating agents has been used for a long time, which reported low- to non-existent complete remission rates and adverse events after prolonged use. Moreover, research into the 13q14 deletion has also provided new insights into the molecular genetics and pathways that interact in such a way, making it possible to transform healthy cells into malignant cells in an entirely new fashion with a complete disregard to its original form, resulting in CLL.
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Various studies have established the prognosis of anemia in myocardial infarction (MI). Both chronic and acute anemia lead to poor outcomes in MI. Regardless, the association of anemia with MI and its management varies. In this study, the literature was analyzed to determine the association between acute anemia and MI based on the pathophysiology, outcomes, and management options. Acute anemia results in decreased blood supply and sudden hypoxia to the heart. Additionally, it exacerbates the preexisting compromised coronary blood supply in patients with MI. Thus, there is a disproportionate oxygen supply and demand ratio to the heart. It was found that anemia increases all-cause mortality in acute MI. However, it is unclear whether anemia is the direct contributor to mortality in these patients. For the management of MI, percutaneous coronary intervention (PCI) is commonly used. Increased incidence of hospital-acquired anemia (HAA) is reported in patients after PCI. However, the cause of HAA in these patients is not well established. Antiplatelet therapy in these patients is also considered to be the culprit for HAA. Nonetheless, no clear evidence is available. There is no consensus or criteria for the treatment of acute anemia in MI patients. Researchers have explored management options such as blood transfusion, erythropoietin-stimulating agent, and iron therapy. Further studies are warranted for a better understanding and management of MI in patients with anemia and vice versa.
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There is a bidirectional relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The liver has a vital role in the pathophysiology of both diseases as it leads to the development of insulin resistance (IR), which in turn results in NAFLD and T2DM. It has been shown that T2DM increases the risk of NAFLD progression. Furthermore, the presence of NAFLD raises the probability of T2DM complications, which explains the increased rates of NAFLD screening in patients with T2DM. In addition, there are common management options for the two diseases. Lifestyle changes can play a role in the initial management of both diseases. Medications that are used to treat T2DM are also used in the management of NAFLD, such as metformin, thiazolidinediones (TZD), glucagon-like peptide-1 (GLP-1) analogues, and dipeptidyl peptidase-4 (DPP4) inhibitors. Bariatric surgery is often used as a last resort and has shown promising results. Lifestyle interventions with diet and exercise are important postoperatively to maintain the weight loss. There are many novel treatments that are being investigated for the treatment of NAFLD, targeting multiple pathophysiologic pathways. This review aims to shed some light on the intricate relationship between NAFLD and T2DM and how IR links both diseases. We also try to raise awareness among clinicians about this relationship and how the presence of one disease should raise a high index of suspicion for the existence of the other.
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Pseudomyopia is an inappropriately excessive accommodation of the eye due to overstimulation or ciliary spasm, which leads to a marked approximation of the far point. Common symptoms of pseudomyopia include eye strain or fatigue, and it is classified as organic or functional. The latter is due to eye strain and functional increase in the ciliary tonus. Pseudomyopia can vary from being a transient condition or continue to progress to myopia. Head trauma is the most common cause followed by psychiatric illnesses, neurologic diseases, and drug-induced causes. There is an association between psychological stress-inducing events and pseudomyopia as it affects the autonomic nervous system. The human body counteracts anxiety by activating the parasympathetic nervous system, causing ciliary muscle contraction. Underlying psychiatric diseases in pseudomyopia patients have been reported in the past in multiple studies. Generalized anxiety disorder is the most common psychiatric illness associated with pseudomyopia with a positive correlation between anxiety-somatization scores and accommodation amount of the eye. It is strongly advised that a psychiatric consultation should be included in the multidisciplinary evaluation of every case. If patients have coexisting anxiety disorders, a multidisciplinary approach using psychiatric consultations, work environment changes, ocular exercises, and cycloplegic drugs can be used. This review aims to shed light on the association of psychiatric disorders such as anxiety with pseudomyopia.
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Exosome-derived microRNA (miRNA) has been the focus of attention in recent years. Mainly, their role in the pathogenesis of different types of cancer has been extensively studied. The different types of exosomal miRNAs (exomiRs) act as either oncogenes or oncosupressors. They have potential prognostic and diagnostic efficacy in different types of cancer due to their high stability and easy detection in bodily fluids. This is especially true in lung cancer, colorectal cancer, ovarian cancer, and breast cancer. However, their efficacy as potential therapies has not been widely investigated. This review will discuss the structure and functions of exosomes and miRNA, as well as the role of exomiRs in the pathogenesis of different types of cancer through boosting growth, promoting progression, chemotherapy resistance, angiogenesis, metastasis, and immune system evasion. We will also discuss the application of exomiRs in diagnosing different types of cancer and their role in prognosis. Furthermore, we shed light on the challenges of developing therapeutic agents using miRNAs and how the carriage of therapeutic miRNA by exosomes can help solve these challenges. Finally, we examine recent studies exploring the potential of exomiRs in treating cancers such as neuroblastoma, glioblastoma, and melanoma.
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Chronic obstructive pulmonary disease (COPD) is a chronic illness that is widely prevalent within the United States and has been frequently associated with heart failure (HF). COPD is associated with progressive damage and inflammation of the airways leading to airflow obstruction and inadequate gas exchange. HF represents a decline in the normal functioning of the heart resulting in insufficient pumping of blood through the circulatory system. COPD and HF present with similar signs and symptoms with some variation. There are many specific diagnostic tests and treatment modalities which we use to diagnose COPD and HF, but it becomes an issue when you come across a patient who has both conditions simultaneously. For example, attempting to use an X-ray to diagnose HF in a COPD patient is next to impossible because the results are manipulated by the COPD disease process. This is the case with many other diagnostic tests such as an electrocardiogram (ECG), chest radiography (X-ray), B-type natriuretic peptide (BNP), echocardiogram, cardiac magnetic resonance imaging (CMR), pulmonary function test (PFT), arterial blood gas (ABG), and exercise stress testing. When a patient has both COPD and HF, it becomes more difficult to treat. Many treatments for HF have negative impacts on COPD patients and vice-versa, whereas some have also shown positive clinical outcomes in both diseases. It is agreeable that treatment has to be patient-centered and it can vary from case to case depending on the severity of the disease. Ultimately, in this review, we discuss COPD and HF and how they interplay in their diagnostic and treatment modalities to gain a better understanding of how to effectively manage patients who have been diagnosed with both conditions.
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Human immunodeficiency virus (HIV) is a part of the lentivirus genus of the retroviridae family that incorporates its genome into the host DNA via a series of complex steps. HIV can be classified into two types, HIV-type 1 (HIV-1) and HIV-type 2 (HIV-2), with HIV-1 being the most common type worldwide. Seventy-six million people have been infected since the start of the pandemic, with a mortality rate of 33 million. Even after 40 years, no cure has been developed for this pandemic. The development of the mRNA vaccine has led to further research for the utilization of mRNA vaccine in HIV, in attempts to create a prophylactic and therapeutic treatment. Although messenger RNA (mRNA) vaccine has been around for many years, it has recently drawn attention due to its role and response in the unforeseen coronavirus pandemic. mRNA vaccine has faced its fair-share of challenges, but it also offers many advantages compared to conventional vaccines such as safety, efficacy, rapid preparation, and versatility. mRNA vaccine has shown promising results and has great potential. In this review, we discuss the types of mRNA vaccine, along with development, delivery, advantages, challenges, and how we are working to overcome these challenges.
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Eclampsia is a common complication of preeclampsia patients and can be life-threatening for both the mother and the fetus. Hence, timely intervention and appropriate management of this detrimental condition are extremely crucial. Eclampsia is described as the occurrence of generalized convulsions in patients with preeclampsia. Magnesium sulfate (MgSO4) is the drug of choice for treating and preventing eclampsia. This review aims to study and analyze the available literature on the pathogenesis of eclampsia, the pharmacology of MgSO4, and its effectiveness in the management of eclampsia. Other proposed treatments and their comparative study with MgSO4 are also discussed. Additionally, we examine the data regarding the impact of eclampsia, its public health burden, and the cost-effectiveness of MgSO4. One of the major drawbacks associated with the use of MgSO4 in low-income countries has been the cost of treatment and the lack of resources. We have analyzed the trials that have proposed alternate treatment regimens which could shape new guidelines to resolve these issues. For this review, we extensively studied abstract and full-text articles from multiple databases. This article discusses the pathophysiology of eclampsia, the pharmacology of MgSO4, the issues surrounding eclampsia management, and how MgSO4 benefits these patients.
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Elevated serum uric acid (SUA) levels have been associated with an increased risk of cardiovascular (CV) disease and acute ischemic stroke (AIS) as well as many other medical conditions. AIS is a CV complication that is the second most common cause of mortality worldwide. It results from reduced blood flow to the brain by means of thrombosis, embolism, or systemic hypoperfusion. Studies have demonstrated an association between SUA levels and CV events, with a significant dose-response relationship between elevated SUA levels and stroke risk. Since the relationship between SUA levels and AIS risk has been established, studies are also being conducted in order to evaluate whether antihyperuricemic drugs can lower this risk. Allopurinol use in hyperuricemic patients has been shown to decrease the risk of major CV events, which include AIS. This narrative review aims to investigate the role of SUA as an independent risk factor for AIS along with the proposed biological mechanisms by thoroughly appraising research findings from relevant full-text articles and abstracts indexed in PubMed and the Cochrane Library. In this literature, we will be discussing hyperuricemia, AIS, the association between the two, and the use of antihyperuricemic medications on stroke prognosis. This review will also shed new light on studies that have begun to provide insight into the predictive role of hyperuricemia in AIS.
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Ischemic heart disease (IHD) is the leading cause of death worldwide, and it is defined as an imbalance between myocardial oxygen supply and demand. Coronary artery disease (CAD) and left ventricular hypertrophy (LVH) are two common causes of IHD that independently result in myocardial ischemia. CAD decreases myocardial blood and oxygen supply whereas LVH increases myocardial oxygen demand. The coexistence of both CAD and LVH results in a significant increase in oxygen demand while simultaneously lowering oxygen supply. Since hypertension is a shared predisposing condition for both CAD and LVH, the left ventricular (LV) mass on noninvasive echocardiography can reflect on the severity of coronary artery stenosis. In clinical practice, it can help physicians decide whether to perform invasive cardiac catheterization to visualize the extent of the coronary block. Although, both CAD and LVH are directly proportional to mortality risk, the addition of eccentric LVH can further increase morbidity and mortality due to myocardial infarction. Therefore, the latest management of both the acute and chronic phases of CAD places an increased emphasis on controlling the predisposing factors to prevent or reverse LVH. For example, angiotensin-converting enzyme inhibitors and diuretics reduce LV mass by lowering the cardiac preload and afterload. This article aims to investigate the deleterious effects of the collaboration between CAD and LVH, establish a causal relationship, and explore the new prevention and management strategies.
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Kisspeptin is a neuropeptide that plays a significant role in human reproduction by its action on the hypothalamic-pituitary-gonadal (HPG) axis and functions through a G-protein-coupled receptor called G-protein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R). It is encoded by the kisspeptin 1 (KISS1) gene that is mainly expressed in the hypothalamus. Kisspeptins are also recognized as vital aspects of maturation and proper function of the reproductive system in both males and females. It also plays its role in the onset of puberty, sexual patterns, desires, ovum development in women, sperm quality in men, feedback mechanisms, pregnancy, and lactation. Studies proved the pathological role of kisspeptin dysregulation in disorders like polycystic ovarian syndrome (PCOS) and infertility. Mutations in the KISS1 gene also contribute to precocious puberty or hypogonadotropic hypogonadism, depending upon the nature of mutations. Levels of kisspeptin also aid in the identification of a few pregnancy-related complications like preeclampsia, intrauterine growth restriction, and act as a marker of miscarriage. Due to the wide range of effects that kisspeptin has on the reproductive axis, investigations are being carried out to develop it as a diagnostic marker, treat diseases like hypogonadism and PCOS, and solve infertility issues.