Current pharmaceutical biotechnology最新文献

Background: Curcuma longa Linn. (Zingiberaceae) is a medicinal plant with significant biological activities owing to curcuminoids (CURs). Nevertheless, its low oral bioavailability because of low water solubility, inadequate absorption, short half-life, and rapid clearance hampered its clinical applications.

Objective: The study aimed to extract, isolate, characterize, and formulate the Phospholipon ®90H complex and evaluate for improved solubility, antiasthmatic and pharmacokinetic potential of CURs.

Methods: Phospholipon®90H-based complex of curcuminoids (CPLC) was synthesized via solvent evaporation technique and reported an improvement of solubility, antiasthmatic, and pharmacokinetic potential of CURs. CPLC was physico-chemically and functionally evaluated by Fourier transforms infrared spectroscopy, differential scanning calorimetry, powder x-ray diffractometry, oral bioavailability, and antiasthmatic activity.

Results: Ethyl acetate rhizome extracts (EARE) displayed ~17.42 % w/w extraction yield of CURs. CPLC revealed high entrapment of CURs (~ 92.55 % w/w) within the polar head of phospholipids. Small particle size ~ 194 nm with zeta potential value ~ -20.4 mV suggests the physical stability of CPLC. Physical analysis evidenced the formation of stable and amorphous CPLC by establishing hydrophobic and weak intermolecular forces between CURs and Phospholipon ®90H. Undoubtedly, the amorphous CPLC raised the aqueous solubility of CURs (~2-fold) compared to pure CURs. CPLC formulations (~ 20 mg/kg of CURs, p.o.) significantly lowered the leucocyte and eosinophil count compared to pure CURs. CPLC improved the oral bioavailability of CURs compared to pure CURs.

Conclusion: Results highlight that CPLC could be established as a breakthrough respiratory nanocarrier for CURs and other phytocompounds with respiratory potential.

Objective: This study aimed to investigate the effect of dihydroartemisinin (DHA) on DU145 cells and the role of NR2F2 (COUP-TFII) and its potential target genes in this process.

Methods: GSE122625 was used to identify differentially expressed genes (DEGs) between the DHA-treated and control groups. Protein-protein interaction (PPI) network analysis was performed to identify hub genes, and the ChEA3 database was used to identify potential transcription factors. qRT-PCR and Western blot were used to validate the expression of genes of interest and functional assays were performed to evaluate the effect of DHA on DU145 and PC-3 cells. To solidify the regulatory relationship of NR2F2 with EFNB2, EBF1, ETS1, and VEGFA, a Chromatin Immunoprecipitation (ChIP) experiment was performed.

Results: We identified 85 DEGs in DU145 cells treated with DHA, and PPI network analysis identified NR2F2 as a hub gene and potential transcription factor. The regulatory network of NR2F2 and its potential target genes (EFNB2, EBF1, ETS1, and VEGFA) was constructed, and the expression of these genes was upregulated in DHA-treated cells compared to control cells. Functional assays showed that DHA treatment inhibited epithelial-mesenchymal transition, reduced inflammation, and promoted apoptosis in DU145 and PC-3 cells. Furthermore, NR2F2 knockdown receded the DHA-induced upregulation of target genes and functional changes of DU145 and PC-3 cells. The outcomes of ChIP unequivocally pointed to a positive regulatory role of NR2F2 in these gene expressions.

Conclusion: Our study suggests that DHA treatment affects the functions of DU145 and PC-3 cells by regulating the expression of NR2F2 and its potential target genes, and NR2F2 may serve as a potential therapeutic target for prostate cancer.

Introduction/objective: This study aimed to examine the effect of a human umbilical cord mesenchymal stem cell-derived exosome (hUC-MSC-Exo) liquid band-aid on wound healing in mice.

Methods: hUC-MSC-Exos were prepared from the supernatant via ion exchange chromatography. The composition ratio of the chitosan liquid band-aid was optimized to form a film and encapsulate hUC-MSC-Exo. The biological effects of chitosan exosome liquid band-aid on human umbilical vein endothelial cells (HUVECs) were observed, and its anti-bacterial properties were tested. BALB/c mice with back skin injury were randomly divided into chitosan exosome liquid band-aid group (CS-Exo), chitosan liquid band-aid group (CS), and normal saline control group (Con), and wound healing was evaluated post-treatment. Skin tissue samples posttreatment were collected for H&E staining.

Results: The hUC-MSC-Exo was prepared and characterized. The optimum conditions for film formation were 1% chitosan solution and 15% poloxamer 407/poloxamer 188 (pH 5.0 ~ 7.0). The chitosan exosome liquid band-aid promoted HUVEC proliferation and migration and markedly inhibited Escherichia coli and Staphylococcus aureus growth in vitro. In vivo, the wound healing rate in the CS-Exo group was higher than that in the Con and CS groups. Fourteen days post-treatment, the wounds completely healed, and hair grew normally, which was consistent with H&E results. Mouse weights in each group did not change significantly after administration, indicating that the chitosan exosome liquid band-aid had no obvious toxic side effects.

Conclusion: Local chitosan exosome liquid band-aid application can promote wound healing in mice, and the mechanism could be related to hUC-MSC-Exo-induced vascular endothelial cell proliferation and migration.

Diabetic neuropathy is a persistent consequence of the biochemical condition known as diabetes mellitus. As of now, the identification and management of diabetic neuropathy continue to be problematic due to problems related to the safety and efficacy of existing therapies. This study examines biomarkers, molecular and cellular events associated with the advancement of diabetic neuropathy, as well as the existing pharmacological and non-pharmacological treatments employed. Furthermore, a holistic and mechanism-centric drug repurposing approach, antioxidant therapy, Gene and Cell therapies, Capsaicin and other spinal cord stimulators and lifestyle interventions are pursued for the identification, treatment and management of diabetic neuropathy. An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer using the keywords "Diabetic Neuropathy", "Biomarkers", "Cellular and Molecular Mechanisms", and "Novel Therapeutic Targets".Thus, we may conclude that non-pharmacological therapies along with palliative treatment, may prove to be crucial in halting the onset of neuropathic symptoms and in lessening those symptoms once they have occurred.

The gut microbiota is a varied population of microorganisms that live in the human gastrointestinal system. Emerging research emphasizes the importance of this microbial ecology in general health and its influence on a variety of disorders. The review explores the synergy between herbal treatment and traditional medicine, emphasizing their cultural significance and therapeutic benefits. It delves into the intricate relationship between herbal remedies, traditional healing practices, and their sustained usage over centuries. The review highlights the pivotal role of the gut microbiota in herbal medicine, elucidating how treatments influence the gastrointestinal microorganisms, impacting overall health. Dietary phytochemicals are underscored for their significance in herbal medicine and nutritional well-being, along with the interdependence of plant extracts and botanicals. The investigation explores the molecular connections between phytoconstituents and gut microbiota, aiming to deepen the understanding of herbal medicine's tailored approach to specific health challenges. The summary concludes by emphasizing herbal treatments' unique ability to regulate gut flora, contributing to overall gastrointestinal wellbeing. In closing, the review provides a concise overview, serving as a valuable resource for integrative medicine research, with recommendations for future exploration of herbal medicine's potential in healthcare.

Ampullaviruses are unique among viruses. They live in extreme environments and have special bottle-shaped architecture. These features make them useful tools for biotechnology. These viruses have compact genomes. They encode a range of enzymes and proteins. Their natural environment highlights their suitability for industrial applications. Ongoing research explores ways in which these viruses can improve enzyme stability. They are also employed in the creation of new biosensors and the development of new bioremediation techniques. High coinfection rates and the ecology of ampullaviruses at larger scales can also reveal new viral vectors. They can also help improve phage therapy. Here, we have explored the structure and function of ampullaviruses. We have focused on their use in biotechnology. We have also identified their characteristics that could prove to be useful. We have also pointed out key knowledge gaps and bridging them could further extend the biotechnological uses.

Background: Anti-Mullerian hormone (AMH) plays a pivotal role in follicular growth and atresia. Recent studies highlighted the role of AMH in attenuating granulosa cell apoptosis and subsequent follicular atresia. Despite the raising understanding of the role of AMH in folliculogenesis, and its contribution to the pathophysiology of certain diseases such as polycystic ovary syndrome, the effect of AMH on the expression of genes regulating folliculogenesis is stills limited.

Objective: This study aims to gain insights into the effect of AMH on atresia regulating genes.

Method: In vivo study was performed on C57BL/6J mice injected with AMH for one month. Thereafter, relative gene expression quantification of Foxo1, Sirt1, p53, Bim, and Bax genes were performed using RT-PCR.

Results: In this study, AMH significantly enhanced the expression of Foxo1 and Sirt1 gene compared to the control group. On the contrary, AMH did not modulate the expression of p53, Bim, or Bax genes. AMH was also found to increase serum FSH and LH levels in a dosedependent manner.

Conclusion: This study demonstrated the capability of AMH to induce Foxo1 and Sirt1 genes. Moreover, our study revealed the role of AMH in elevating LH serum level which is a main contributor to the pathophysiology of polycystic ovary syndrome, opening new avenues for the study of AMH as a main contributor to the stalled follicular atresia and growth associated with the disease.

Perioperative Neurocognitive (PND) disorders represent a prevalent complication among geriatric patients, manifested in diverse forms of cognitive impairment following anesthesia and surgical procedures. Even though the exact origin of PND disorders is still unknown, neuroinflammation has been identified as a significant contributing factor, particularly in older patients. Hence, this review aims to provide a deeper insight into the underlying mechanism and associated potent therapeutic targets for the efficient management of perioperative neurocognitive disorders. Many factors, such as PRRs, chemokine receptors, immunoglobulin superfamily receptors, and purinergic receptors, are involved in the development and occurrence of perioperative neurocognitive disorders to varying degrees and may be valuable biomarkers for their effective management. Here, we present a comprehensive overview of the involvement of neuroinflammation in PND disorders, including their onset and possible therapeutic targets. This review would benefit future researchers in elucidating a better therapeutic approach for the management of perioperative neurocognitive disorders. We have also briefly outlined the clinical trials associated with Postoperative neurocognitive disorders in the last section of the review. Altogether, this review would help the researchers investigate better therapeutics for the management of PND disorders.

The incidence of Coronavirus Disease 2019 (COVID-19) has increased dramatically in recent years, affecting millions of people worldwide. The primary cause of morbidity and mortality in COVID-19 patients is respiratory illness. However, the disease can also significantly impact the cardiovascular system. SARS-CoV-2, the virus responsible for COVID-19, enters cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. ACE-2 is a component of the renin-angiotensin system (RAS) and plays a crucial role in regulating various pathological processes. The interaction of the virus with ACE-2 in the myocardium can lead to direct heart damage. Several mechanisms may contribute to myocardial damage in COVID-19 patients, including systemic inflammation, myocardial interstitial fibrosis, interferon-mediated immune response, exaggerated cytokine response, T-cell-mediated damage, coronary plaque instability, and hypoxia. There has been concern that ACE inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression. However, it may be advisable to continue medications for patients with underlying cardiovascular disorders. The precise mechanisms of cardiomyocyte injury in COVID-19 are not fully understood, but necroptosis appears to play a significant role. Current treatments for cardiac damage in COVID-19 patients include IL-6 blockers and antiplatelet therapy. Ponatinib, a small molecule tyrosine kinase inhibitor designed using computational and structural approaches, has shown the potential to affect cell death through its impact on tyrosine kinase activity. By reviewing studies related to ponatinib's effects on necroptosis and cell death, we propose a novel approach to potentially reduce the cardiotoxic effects of COVID-19 on cardiomyocytes. Further research is needed to fully elucidate the mechanisms of cardiac injury in COVID-19 and to develop targeted therapies to protect the heart from the devastating effects of this disease.

Type 2 diabetes mellitus is a serious metabolic disease having a high growth rate and becoming a global threat. An unhealthy lifestyle, food intake, and genetic susceptibility are the major factors responsible for this metabolic disorder. This disease results in hyperlipidemia, hyperglycemia, glucose intolerance, restricted insulin synthesis, and insulin resistance. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising approach to diabetes focuses on gut microflora and their associated metabolites. Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology. This study explores the dysbiosis in the human gut microflora in Type 2 Diabetes Mellitus and how the gut microbiota influences metabolites related to T2DM. It also sheds light on early identification and targeted intervention for this. Understanding these mechanisms could potentially lead to more effective strategies for managing and preventing T2DM. The findings of our literature study are that gut microbiota can serve as biomarkers for early disease detection. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to emphasize the improvement of T2DM progression.