Current pharmaceutical design最新文献

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.

Introduction: Keloid scars and hypertrophic scars both cause abnormal protrusions or depressions on the skin surface, some of which may develop noticeable discoloration that significantly affects aesthetic appearance, leading to psychological distress and impacting the patient's overall well-being. Currently, there are still no effective treatment methods available. Among the various mechanisms involved in scar treatment, most studies focus on regulating the activity of fibroblasts. However, current research also suggests that inflammation plays a significant role in the healing process of scars. Glycyrrhetic Acid (GA) is a natural sweetener found in licorice root and is widely used as a sweetening agent in various plants worldwide. In our previous studies, we found that GA exhibits potential anti-scarring effects in animals, but the underlying mechanisms remain unclear.

Methods: We employed a combination of animal experiments, transcriptomics, network pharmacology, molecular docking, and molecular dynamics simulations to explore potential mechanisms. The expression of relevant genes and proteins was validated through qRT-PCR and protein detection.

Results: The results showed that GA promotes scar healing in a dose-dependent manner. Compared with the model group, the GA treatment group inhibited the expression of inflammatory factors IL-6 and IFN-γ in rat scar tissue, down-regulated the expression of CDK1, a cell cycle-related protein, and the expression of MKI67, a proliferation marker.

Conclusion: Finally, we concluded that GA promotes the recovery of rat skin scars by regulating the balance of inflammation and fibroblast proliferation.

Introduction: To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

Methods: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

Results: SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiotatargeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

Discussion: The findings show that, among other factors, gut metabolites-such as uremic toxins, bile acids, TMAO, and SCFAs - are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

Conclusion: The gut microbiota significantly influences the hepato-cardiorenal axis through metabolitemediated signalling. While therapeutic modulation shows promise, precision medicine approaches and highquality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.

Introduction: For centuries, Traditional Chinese Medicine has been a subject of extensive research for its healing properties, including its effects against viruses. The pollen of Typha angustifolia emerges as a notable natural source of antiviral agents, with earlier investigations focusing on its antioxidant and antiinflammatory properties, which are associated with flavonoids and phenolics that facilitate electron transfer. These bioactive compounds could potentially disrupt viral entry and replication, thereby necessitating further studies.

Methods: Molecular docking analysis was conducted on 11 compounds from T. angustifolia targeting the entry protein of dengue virus, the NS5B polymerase of hepatitis C virus, and the RdRp of Japanese encephalitis virus. The binding affinity was evaluated through LibDock score assessments, and simulations of molecular dynamics (RMSD and RMSF) were performed to analyze the stability of the complexes.

Results: Naringenin was consistently identified as one of the highest binders for all three viral proteins, achieving the top score for the RdRp of Japanese encephalitis (129.288). Isorhamnetin showed the greatest binding affinity for the hepatitis C NS5B polymerase (120.827), exceeding that of sofosbuvir (120.629), while isorhamnetin-3-O-rutinoside displayed strong binding to the dengue viral entry protein (97.0838). Molecular dynamics confirmed the stability of ligand-protein interactions, underlined by sustained van der Waals and electrostatic forces.

Discussion: These findings underscore naringenin as a versatile antiviral candidate, with other flavonoids exhibiting specific effectiveness that could facilitate multitarget inhibition approaches. This polypharmacological potential of flavonoids aligns with their established antiviral properties, although confirmatory experimental studies are critical.

Conclusion: Naringenin emerged as the most potent and reliable antiviral agent among the compounds of T. angustifolia, particularly against the RdRp of Japanese encephalitis. These computational insights validate T. angustifolia pollen as a promising natural antiviral resource, warranting further validation through in vitro and in vivo studies.