Cardiovascular & hematological disorders drug targets最新文献

Introduction: Tattooing, which is becoming more and more widespread in the world, makes it necessary to care about the long-term health consequences of tattoo ink exposure and its potential association with skin and lymphatic carcinogenesis.

Methods: A narrative review was performed by searching peer-reviewed articles in PubMed written up to the year 2025. The search words were "tattoo ink," "skin cancer," "lymphoma," "tattoo-associated malignancy," "carcinogenic pigments," "polycyclic aromatic hydrocarbons (PAHs)," "heavy metals in tattoo inks," and "nanoparticle migration." Papers were chosen for their relevance to the composition, migration of pigments, toxicological mechanisms, and documented associations with cancer.

Results: Tattoo inks may contain substances such as PAHs, azo dyes, titanium dioxide, and heavy metals. It is possible for these particles to deteriorate with UV illumination and migrate to lymph nodes, causing chronic inflammation and oxidative stress. Imaging demonstrates the nanoparticle localisation within lymphatic organs, whereas toxicological studies associate genotoxicity and immune damage with components of the pigment. There are a few clinical case reports and a few population-based studies indicating a potential relationship with lymphoma and skin malignancies.

Discussion: While causality has not been proven, supportive evidence across toxicologic and clinical spheres suggests a biologically plausible risk for cancer. Limitations of this study are heterogeneity in design and ink, as well as the absence of long-term cohort data. Regulatory and labelling requirements are also not well synchronized across the world.

Conclusion: At the chemical and biological level, exposure to tattoo ink can increase the risk of carcinogenesis. Additional research and more stringent regulations are needed to establish and mitigate potential long-term health risks.

Plasma lipoprotein(a) [Lp(a)] levels greater than 50 mg/dL are an independent risk factor for cardiovascular diseases, including heart failure, atherosclerosis, and aortic valve stenosis. Lp(a) exhibits proatherogenic properties by promoting vascular inflammation, thrombosis, and calcification. Several therapeutic agents specifically designed to reduce Lp(a) formation are currently under evaluation in clinical trials or regulatory review. Muvalaplin is notable as the first orally administered drug developed to lower plasma Lp(a) levels. This review evaluates the efficacy, safety, and tolerability of muvalaplin and compares its profile with other Lp(a)- lowering agents. A systematic literature search was conducted using the PubMed database for articles published between 2020 and 2025, with keywords, including muvalaplin, lipoprotein, and cardiovascular. Only original research, clinical trials, and review articles were included. Muvalaplin is an oral small-molecule inhibitor being studied as the first oral Lp(a)-lowering agent. In Phase I trials, daily administration of muvalaplin for 14 days reduced Lp(a) levels by up to 65%. In Phase II trials, 12 weeks of daily muvalaplin resulted in reductions of up to 86% in Lp(a) levels without significant safety or tolerability concerns. These findings suggest that muvalaplin could be a valuable therapeutic option for managing cardiovascular risk associated with elevated Lp(a). Notably, unlike other Lp(a)-lowering agents, muvalaplin did not cause skinrelated adverse events at injection sites. Although the initial clinical data are promising, Phase III trials are required to establish long-term safety and determine whether reductions in plasma Lp(a) translate into meaningful reductions in cardiovascular events.

Background: The 36-amino acid peptide known as neuropeptide Y (NPY) is widely expressed in both the central and peripheral nerve systems and is essential for regulating energy balance, stress responses, cardiovascular function, and immunological regulation through Gprotein- coupled Y receptors (Y1, Y2, Y4, Y5).

Objective: To explore the various functions of NPY in hematological and cardiovascular disorders and investigate potential therapeutic approaches that target NPY signaling networks.

Methods: A comprehensive literature analysis focused on NPY-mediated mechanisms in cardiovascular diseases (CVDs) and hematological disorders. The review highlights pharmacological modulators, including synthetic analogs, receptor-specific agents, enzyme inhibitors, and natural substances.

Results: NPY dysregulation promotes vasoconstriction and inflammation, particularly through Y1 receptor activation, contributing to diseases such as atherosclerosis, heart failure, and hypertension. In hematological disorders, NPY influences hematopoiesis, immune cell activity, and angiogenesis, affecting conditions such as thrombosis and leukemia. Therapeutic approaches include receptor-specific agonists and antagonists (e.g., [Leu31, Pro34]NPY, BAY 53-6206), enzyme inhibitors (DPP4, NEP), and natural substances (flavonoids, polyphenols, saponins). Although therapeutic resistance remains a challenge, glucocorticoids also affect NPY expression.

Conclusion: NPY acts as a crucial modulator in hematological and cardiovascular disorders. Understanding its receptor-specific functions enables the development of targeted therapeutic strategies. Natural substances provide promising adjuncts for modulating NPY activity, supporting integrated approaches for treating NPY-related disorders.

Introduction: Duchenne Muscular Dystrophy (DMD) is a rare X-linked recessive disorder caused by mutations in the dystrophin gene, leading to progressive muscle weakness. Cardiomyopathy and respiratory failure remain leading causes of mortality despite improvements in respiratory, cardiac, and pharmacological management. This review aims to summarize current knowledge on the pathophysiology, management strategies, and emerging therapies for DMD-associated dilated cardiomyopathy.

Methods: A comprehensive literature search was performed for studies published up to May 2025 using PubMed, Scopus, Web of Science, and Google Scholar. Keywords included "Duchenne Muscular Dystrophy," "Dilated Cardiomyopathy," "gene therapy," "disease management," "pathophysiology," and "therapeutics," combined with Boolean operators (AND, OR). Eligible studies were in English, methodologically robust, and focused on DMD pathophysiology, clinical management, and therapeutic advances.

Results: Recent research has advanced the understanding of dilated cardiomyopathy in DMD. Progress includes gene therapy, exon-skipping, and interventions targeting mitochondrial dysfunction, calcium imbalance, and fibrosis, all showing promising preclinical outcomes. Multidisciplinary care approaches have extended survival and improved quality of life.

Discussion: Dystrophin deficiency drives inflammation, oxidative stress, and myocardial remodeling in DMD cardiomyopathy. While supportive management is effective in delaying progression, access to advanced therapies is inconsistent, and curative treatments remain elusive.

Conclusion: Long-term management benefits from early diagnosis and coordinated care involving neurology, cardiology, pulmonology, and rehabilitation. Continued research into targeted molecular interventions holds promise for improved outcomes in DMD-associated cardiomyopathy.

Introduction: Human immunodeficiency virus (HIV) has emerged as a cause of morbidity and mortality worldwide. HIV positive patients commonly suffer from various hematological abnormalities of all lineages, which are diverse and can occur at any stage of infection. Hematologists should be aware of bone marrow changes associated with retroviral disease (RVD) so that appropriate and prompt treatment can be given to these patients.

Methods: The study was carried out in the department of clinical pathology of a tertiary care hospital for the duration of 1 year, from January 2023 to December 2023. Out of a total of 90 bone marrow received, 20 patients were retrospectively studied for morphological changes in bone marrow who were HIV positive on ELISA and confirmed on Western blot.

Results: The age range of the study population was 22 to 60 years. There was a predominance of male participants (85%). The predominant hematological abnormality on peripheral smear was anemia (90%). Microcytic hypochromic type of anemia was the most frequently observed finding. The bone marrow was hypercellular (70%) in most cases. Erythroid hyperplasia was seen in 14 cases. Erythroid normoblastic maturation was predominant (70%). Dysplasia was noted in 12 cases out of 20 cases, with isolated erythroid dysplasia (25%) being the most common. Reactive changes associated with HIV were also observed. In addition, we also reported one case of autoimmune hemolytic anemia and another of visceral leishmaniasis, both associated with HIV infection.

Conclusion: A bone marrow study, along with a detailed approach to all relevant possible contributors and clinical history, should be considered for the diagnostic approach in documenting peripheral hematological abnormalities, opportunistic infections, and malignancies in HIV positive patients.

Introduction: The present study aimed to investigate the cardioprotective effect of Borago officinalis and its synergistic effect against isoproterenol-induced myocardial infarction in Sprague-Dawley (SD) rats.

Materials and Methods: Myocardial infarction was experimentally induced in SD rats (Rattus norvegicus) using subcutaneous administration of isoproterenol (ISO) 85 mg/kg/s.c on days 20 and 21. Experimental animals were divided into five groups (5 animals each): normal control (NC), negative control (ISO), test drug Borago officinalis leaf extract (BOL) group, standard drug metoprolol (SDG) group, and combination of test drug Borago officinalis and standard drug metoprolol (BOM) group. Physical (heart grading and heart/body weight ratio), biochemical (CK-MB, LDH, AST, and ALT), troponin, oxidative stress (TBARS), and antioxidant parameters (SOD, CAT, GSH, and GPx) were assessed. Additionally, histopathological analysis of heart tissues was performed.

Results: ISO significantly impaired cardiac function, as indicated by elevated biochemical markers (CK-MB, LDH, AST, and ALT) and oxidative stress markers (TBARS), and by heart tissue damage, with lowered antioxidant parameters (SOD, CAT, GSH, and GPx). Rats pre-treated with BOL, SDG, or their combination, BOM, effectively reduced these effects. Among them, the BOM group showed a significant cardioprotective effect, suggesting a synergistic action that outperformed metoprolol alone.

Discussion: Rats that were pre-treated with Borago officinalis extract showed significant improvement in biochemical, antioxidant, and histopathological markers compared to the rats in the ISO group. However, the combination of Borago officinalis and metoprolol provided the most pronounced protection, suggesting a synergistic effect.

Conclusion: The findings of the present study highlight the potential of Borago officinalis as a complementary cardioprotective agent.

Introduction: Due to the lack of sufficient studies on the mechanisms of the cardiovascular effects of Berberis vulgaris (B. vulgaris), this study aimed to evaluate the cardiovascular effects of the hydroalcoholic extract of B. vulgaris fruit on nitric oxide (NO) and acute hypertension caused by NG-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor).

Methods: In total, 48 male rats were assigned to six groups (n = 8): the control group, which received saline intraperitoneally (i.p), the L-NAME group, which received L-NAME intravenously (10 mg/kg. i.v), the L-NAME + SNP group, which received sodium nitroprusside (SNP, 50 μg/kg, i.p), followed by L-NAME after 30 min, and three treatment groups, which received the B. vulgaris extract at concentrations of 100, 200, and 400 mg/kg, followed by L-NAME. The heart rate (HR), mean arterial pressure (MAP), and systolic blood pressure (SBP) were measured up to 30 min after L-NAME injection. Afterward, changes (Δ) in SBP, MAP, and HR were calculated and analyzed.

Results: All doses of the extract attenuated ΔSBP, ΔMAP, and ΔHR; however, these changes in the groups receiving the extract at the doses of 200 and 400 mg/kg were significantly lower than in the group receiving saline (P < 0.05-P < 0.01, respectively). In the L-NAME group, ΔSBP, ΔMAP, and ΔHR were significantly increased (P < 0.01-P < 0.001). In the L-NAME + SNP group, all responses were significantly lower than in the L-NAME group (P < 0.01-P < 0.001). The extract at the doses of 200 and 400 mg/kg significantly reduced ΔHR, ΔMAP, and ΔSBP induced by L-NAME (P < 0.05-P < 0.001). Moreover, these changes at the doses of 100 and 200 were significantly higher than in the L-NAME + SNP group.

Discussion: In the present study, it was demonstrated that the dose of the B. vulgaris extract dependently decreased cardiovascular parameters in basal and L-NAME-induced hypertensive conditions. This response suggests that the cardiovascular effect of the hydroalcoholic extract of B. vulgaris is partly mediated by an increase in NO production. Given the vasodilatory effect of NO, it seems that NO reduces vascular resistance and causes a decrease in blood pressure.

Conclusion: NO has a beneficial effect on the cardiovascular system, and the hypotensive effect of B. vulgaris extract is partly mediated by increased NO production.

Congenital atransferrinemia is an extremely rare autosomal recessive disorder characterized by functional or quantitative deficiency of transferrin. This leads to a characteristic clinical picture that includes heart failure due to iron overload cardiomyopathy, severe anemia, as well as hepatic and endocrine dysfunction in early infancy. Although rare or may be underdiagnosed, congenital atransferrinemia is a treatable cause of infantile heart failure and iron overload cardiomyopathy. Therefore, it is important to keep this diagnosis as a possibility in childhood presentation of heart failure and anemia. Early diagnosis and timely treatment can prevent progressive myocardial dysfunction and recurrent heart failure. This article focuses on pathophysiology, diagnosis, genetics, and management of heart failure in congenital atransferrinemia.

Introduction: Acute lymphoblastic leukemia (ALL) in adult patients usually poses a treatment challenge with intensive chemotherapeutic agents. Prognosis is worse in comparison to pediatric patients owing to disease biology and associated comorbidities. Spontaneous remission of ALL is rare and warrants close follow-up for progression.

Case presentation: Herein, we report the case of a male in his 40s initially admitted for febrile illness with pancytopenia; later, his serology was positive for scrub typhus infection, and he was managed for the same with antimicrobials. Due to the persistence of pancytopenia, a bone marrow examination revealed 14% blasts, which were confirmed as B lymphoblasts on flow cytometry. Molecular workup, including cytogenetic and next-generation sequencing, was done. There was no indication for treatment, and the hemogram subsequently improved spontaneously, with normalization of blood count parameters.

Conclusion: The patient was kept under close follow-up as an outpatient with clinical examination and hematological parameters. Five months later, the patient was diagnosed with ALL and, unfortunately, died during therapy.

Background: Elevated levels of lipoprotein(a) have been linked to an increased risk of Atherosclerotic Cardiovascular Disease (ASCVD). Conventional lipid-lowering medications have modest to no impact on Lp(a) levels. Emerging RNA-based modalities significantly decrease Lp(a) by silencing the apo(a) mRNA at the post-transcriptional level. Pelacarsen (TQJ230) is a GalNAc-conjugated novel Antisense Oligonucleotide (ASO) that selectively inhibits apo(a) synthesis in hepatocytes.

Objective: This updated review aims to elucidate the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of Pelacarsen (TQJ230), with a focused appraisal of its potential role in the prevention of Atherosclerotic Cardiovascular Disease (ASCVD).

Methodology: We conducted a literature search on PubMed, Google Scholar, and Scopus using keywords such as "Pelacarsen", "antisense oligonucleotide" OR "ASO", and "lipoprotein(a)" from inception to March 2025.

Results: Pelacarsen demonstrated a dose-dependent sustained reduction in Lp(a) levels, achieving up to a 97% reduction at the highest dose in Phase 1 and 2 trials. It was well-tolerated with a favorable safety profile. Phase 3 trials are underway to provide robust data on its long-term safety and impact on Atherosclerotic Cardiovascular Disease (ASCVD) outcomes.

Conclusion: Pelacarsen (TQJ230) is a potent Lp(a)-lowering agent with promising efficacy and a favorable safety profile. However, its definitive role in reducing atherosclerotic cardiovascular events remains to be established. Ongoing Phase 3 trials will be critical in determining whether its lipid-lowering effects translate into meaningful long-term cardiovascular outcomes.