Current pharmaceutical design最新文献

Heart failure (HF) is a critical global health concern, affecting women due to unique biological, epidemiological, and sociocultural factors. Despite accounting for a significant percentage of cardiovascular disease (CVD) mortality among women, HF remains unexplored, particularly in areas such as gender-specific diagnostic challenges and therapeutic strategies. This review explores the intricate pathophysiology of HF, focusing on inflammation, oxidative stress, endothelial dysfunction, and fibrosis as pivotal contributors to disease progression. Moreover, it highlights advancements in pharmacological treatments, including ARNI, SGLT2 inhibitors, and novel therapeutic agents like vericiguat (for selective patients) and omecamtiv mecarbil (modest benefits), while addressing the potential of lifestyle interventions, such as diet, exercise, in mitigating HF risk. Artificial intelligence emerges as a promising potential for enhancing diagnostic precision, patient management, and outcome prediction, heralding a new era in HF care. By integrating gender-specific research and innovations, this study aims to refine strategies for improving women's cardiac health, ultimately reducing the global burden of HF.

Pulmonary drug delivery systems have emerged as non-invasive and effective platforms for treating intrapulmonary and extrapulmonary conditions, allowing for direct drug administration to the lungs or systemic delivery via pulmonary absorption. The lungs' large surface area and extensive alveolar network facilitate rapid absorption of drugs at high concentrations, allowing for lower dosing, reduced systemic side effects, and improved therapeutic outcomes through targeted delivery. Nanotechnology further enhances pulmonary drug delivery systems by encapsulating drugs in nanoparticles, which can improve drug stability, promote cellular uptake, enable passive targeting, and offer controlled release profiles. With the increasing incidence of respiratory diseases and growing interest in pulmonary delivery for both local and systemic therapy, a deeper understanding of respiratory drug delivery mechanisms is critical. This review provides a comprehensive overview of pulmonary drug delivery systems, beginning with conventional delivery systems and their clinical applications. It then examines the challenges affecting the efficacy of inhaled therapies and explores recent advancements, particularly nanoparticle formulations, that aim to improve drug targeting, bioavailability, and patient adherence. The review concludes by highlighting ongoing challenges and outlining future perspectives for the development of more efficient and patient-centric pulmonary drug delivery strategies. Ultimately, nanoparticle-based systems offer a promising alternative for improving the treatment of pulmonary and systemic infections, supporting better patient outcomes and advancing precision respiratory medicine.

Introduction: Head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC), is an aggressive malignancy with poor survival rates due to late diagnosis and recurrence. This study aims to identify novel biomarkers and therapeutic targets to improve early detection and treatment, ultimately enhancing patient outcomes and reducing mortality associated with HNSCC and OC.

Method: This review explores the major cross-talking signals, drugs, and target genes of HNSCC and OC, with a focus on Wnt as a key resource. Keywords in OC studies were categorized, revealing highly specific pathways and the role of pharmacogenomics, nutrigenomics, and gene mutations for future drug development.

Results: The roles of interlinked signaling pathways and gene networks in HNSCC and OC, identifying major regulatory pathways as potential therapeutic targets, and discussing target genes and therapies.

Discussion: Understanding molecular pathways is crucial for precision medicine in OC Integrating pharmacogenomic and nutrigenomic insights can improve therapeutic outcomes and reduce toxicity, despite resistance and heterogeneity challenges.

Conclusion: This review focuses on HNSCC and OC, both of which are complex diseases with multiple molecular mechanisms. Understanding the cross-talk between signaling pathways is crucial for identifying novel therapeutic targets. Despite advancements in modern medicine and synthetic drugs, herbal remedies continue to be used in healthcare and can effectively support therapy in various ways. Biological therapies, such as monoclonal antibodies, can help reduce the side effects of chemotherapy, whereas synthetic drugs have posed challenges in recent years.

According to the World Health Organization, Anemia is a health concern that impacts a substantial number of individuals globally, with 50% of cases due to iron deficiency and the remaining 50% being caused by other conditions and vitamin deficiencies. Iron deficiency anemia can cause several health issues, such as weakness, exhaustion, poor cognitive function, and a higher chance of pregnancy difficulties. Iron supplementation, particularly through dietary sources and supplement formulations, is fundamental in addressing this condition and is favored for managing mild to moderate cases. Ferrous and ferric iron are two types of iron that are often employed. Ferric pyrophosphate is a novel compound, complexed with pyrophosphate, is directly absorbed in the intestine, particularly by M cells in the duodenum. Ferric pyrophosphate is favored due to its higher elemental iron content, superior bioavailability, tolerability, and minimal impact on food color, taste, and texture. This review offers an in-depth investigation of ferric pyrophosphate as an alternative therapy for iron deficiency anemia because no review article currently available has compiled the research trends, benefits, and drawbacks of this drug. It summarizes pre-clinical and clinical studies on ferric pyrophosphate, exploring its pathogenesis, chemistry, safety, and efficacy.

Cannabidiol (CBD), one of the compounds found in cannabis sativa, has drawn a lot of interest in the study and treatment of epilepsy. The antiepileptic qualities of CBD are being investigated for their ability to reduce seizure frequency and intensity in people with rare epilepsies, including West syndrome, Ohtahara's syndrome, Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis. This review attempts to analyze the antiepileptic effects of cannabidiol against voltage-gated calcium channel T-type (CaV), GammaAminobutyric Acid A (GABAA), voltage-gated potassium channel of the Q family (KCNQ2), voltage-gated sodium channel (NaV), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) using in silico techniques. Studies were conducted to investigate Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters, and subsequently, molecular docking was performed. CBD demonstrated good oral absorption and the ability to cross the blood-brain barrier, as indicated by its pharmacokinetic parameters. The CBD may lead to potential drug interactions and increased bioavailability of the molecule due to metabolic interactions with the cytochrome P450 enzymatic system. CBD did not present toxicity parameters evaluated in this work. The molecular docking of CBD showed good interactions with NMDA and Nav. It also demonstrated good binding energy.

Personalized medicine or precision medicine is a holistic approach to combat with patient's disease through their individual characteristics. This includes genetic makeup, lifestyle, and environmental influences. In addition to this, personalized medicine offers several advantages such as saving time, being cost-effective, and improving patient compliance. Looking at these benefits, researchers have explored personalized medicines in several diseases such as cardiovascular disease, neurodegenerative disease, and cancer. Furthermore, to ensure safety, efficacy, and quality of therapeutic treatments, regulatory guidelines are essential for evolving technologies and advancement in the field of personalized medicine. Various regulatory authorities play an important role in the regulation of personalized medicine in India, including CDSCO, ICMR, DBT, and PCI. Regulation of these guidelines ensures the protection of patients' safety by developing new treatments that require robust testing and clinical trials to assure the effectiveness and identify potential risks. The present review covers a brief introduction on personalized medicine and its history, the need for personalized medicines, tools used in personalized medicine, the importance of regulatory guidelines, Regulatory bodies in India, Challenges in personalized medicine, role of AI in overcoming obstacles in the path of personalized medicines, possible solutions, and future aspects.

Mucosal melanoma (MM) is a potentially lethal malignant neoplasm arising in the respiratory, gastrointestinal, and urogenital tracts. MM comprises less than 2% of all melanomas, and no increase in its incidence has been reported. The etiopathogenesis of mucosal melanoma is uncertain. Whenever feasible, complete surgical excision is the treatment of choice for patients with regional disease. The clinical utility of routine lymph node sampling and completion lymph node dissection in patients with mucosal melanoma remains uncertain. Immune checkpoint inhibitors have become the standard-of-care for cutaneous melanoma. However, the biology of MM differs from that of cutaneous melanoma. Thus, the intensity of the response of MM is somewhat lower than that of cutaneous melanoma. This editorial highlights the recent advances in the treatment of mucosal melanoma.

Introduction: The current study aimed to synthesize and identify the biological activities of pyrazine- piperidine amide pharmacophore derivatives against non-small lung carcinoma (Calu-6) cells.

Methods: The combinatorial formulation was prepared by an active mixture of different chemical substituents, and five (6A-E) different molecules were synthesized. The chemical structures were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (H1) spectroscopy.

Results: These compounds were also screened for cytotoxicity against the Calu-6 cell line. Compounds 6B and 6D displayed potent cytotoxicity, with IC50 Values of 45.21 μM and 89.64 μM, respectively. Cellular uptake and apoptotic studies using compound microscopy and flow cytometry revealed that cell damage gradually increased, leading to cell death. Compound 6B at 25 μM and 50 μM had 75.3% and 65.3% viability, 8.61% and 9.85% apoptotic effects, 12.05% and 21.4% late apoptosis, and 4.02% and 3.4% necrosis, respectively.

Discussion: Compound 6B was found to significantly enhance cell cycle arrest at the G2/M phase. Additionally, real-time RT-PCR and western blot analyses further confirmed the enhanced expression of apoptotic markers, such as caspase-3 and 8, as well as the antiproliferative gene p53.

Conclusion: These findings indicate that compound 6B has a promising anticancer effect on lung cancer.

Introduction: Bixie Shenshi Decoction (BSSD), a traditional Chinese herbal formula, has long been used to treat inflammatory skin conditions. This study aimed to investigate the therapeutic effects of BSSD on psoriasis-like mouse models and elucidate its underlying mechanisms.

Methods: We evaluated inflammatory factors and signaling pathways via Western blot and RT-qPCR in mouse models. HPLC-MS was used to analyze BSSD components, while network pharmacology combined with database mining predicted its target pathways.

Results: BSSD treatment improved psoriatic skin lesions, reduced epidermal hyperproliferation, and reduced levels of pro-inflammatory cytokines in skin tissue and plasma. Additionally, BSSD decreased phosphorylation of STAT3 and Akt in mouse skin lesions. Network pharmacology analysis revealed that BSSD's targets were primarily enriched in the Th17 signaling pathway and metabolic pathways, with IL-6, TNF, ESR1, CASP3, TP53, and MMP9 identified as core targets. Molecular docking predicted the binding interactions between these targets and BSSD compounds.

Discussion: BSSD's multi-target mechanism aligns with psoriasis pathogenesis. By integrating multicomponent, multi-target modulation, BSSD offers a complementary approach to single-target therapies, which are limited by a narrow focus on individual disease drivers.

Conclusion: BSSD exerts therapeutic effects against psoriasis by targeting key biological factors and inhibiting the activation of the JAK/STAT3 and PI3K/Akt pathways.

Pruritus, or itching, is a bothersome symptom linked to many skin and systemic disorders, significantly impacting patients' lives. Traditional treatments like antihistamines and corticosteroids often fall short, causing systemic side effects and delivering less than optimal results. Nanotechnology, particularly using nanoparticles, provides a highly sophisticated approach to drug delivery. Nanoparticles enable targeted delivery of therapeutic agents by recognizing and binding to cellular receptors or inflammatory pathways associated with pruritus. To enhance drug penetration and retention in the skin, spherical lipid bilayer vesicles, known as liposomes, can encapsulate hydrophilic and lipophilic drugs. This technology maximizes therapeutic benefits while minimizing systemic absorption and toxicity. Microneedle systems, another advanced technology, use arrays of tiny needles to painlessly penetrate the skin and deliver drugs directly to the dermal layer. This method enhances drug bioavailability and allows for localized pruritus treatment with minimal discomfort and side effects. New therapies are investigating novel drug formulations and molecular targets, with clinical trials evaluating the effectiveness of these advanced delivery systems in the management of pruritus. Pharmacogenomics and precision medicine further customize treatment protocols by tailoring therapies to individual genetic profiles and specific pruritus causes. These approaches promise more effective, patient-centric care, ultimately improving therapeutic outcomes and the quality of life for those suffering from pruritus. Overall, targeted drug delivery systems are transforming pruritus treatment, providing a more refined and effective way to manage this challenging symptom.