Current pharmaceutical biotechnology最新文献

Objective: The aim of this study was to elucidate the causal relationship between the consumption of processed and red meats (specifically pork, beef, and mutton) and susceptibility to various lung cancer types.

Background: Previous observational studies have indicated a potential cancer risk associated with red and processed meat consumption. However, a clear causal relationship remains undetermined.

Purpose: Refining the study of the association between processed and red meat and lung cancer using a Mendelian randomization study.

Method: We harnessed the robustness of Two-Sample Mendelian Randomization, integrating data from the esteemed UK Biobank, capturing dietary habits with oncological datasets from the Transdisciplinary Research In Cancer of the Lung. The analytical approach was anchored in the inverse variance weighted (IVW) method, enriched by sensitivity analyses for result validation.

Result: Genetic predispositions favoring processed meat consumption are linked to heightened risks of lung cancer [IVW analysis, OR=1.8203, 95%CI [1.1115,2.9811], p=0.0173], and in LUSC [IVW analysis, OR=2.9274, 95%CI [1.4810,5.7863], p=0.0020]. Beef was more important in lung cancer [IVW analysis, OR=4.6739, 95% CI [2.4947, 8.7570], p=0.000001], in LUSC [IVW analysis, OR=3.3251, 95%CI [1.2055,9.1717], p=0.0203] and in LUAD [IVW analysis, OR=7.1480, 95%CI [3.0074,16.9893], p=0.000008]. However, no significant links were identified between mutton or pork intake and lung cancer.

Conclusion: Processed meat and beef consumption may elevate lung cancer risk. Additional research is warranted to investigate potential links between mutton or pork consumption and the risk of lung cancer.

Objectives: Polygonati rhizoma (PR) has been used for thousands of years to alleviate dementia. Here, we aimed to elucidate the effect of alleviating vascular dementia (VaD) and underlying mechanism of PR.

Methods: In vivo, rats were treated with two-vessel occlusion (2VO) induces VaD. The anti-VaD effect measured by learning and memory capacity, cerebral pathological structure, and cerebral microglial M1/M2 phenotype biomarkers. Subsequently, screening potential mechanisms of PR for VaD using network pharmacology and molecular docking methods. Moreover, the efficacy of PR-contained serum on LPS-induced inflammation and polarization on BV2 microglia was evaluated with NF-κB/NLRP3 pathway.

Results: In vivo, PR significantly enhanced learning and memory capacity, suppressed M1 microglia activation and promoted M2 polarization. Through network pharmacology and molecular docking approaches, we screened inflammation as a potential mechanism for PR anti-VaD, with targets involving NF-κB. Meanwhile, PR could regulate the expression of NF-κB/NLRP3 pathway compared with that of LPS-induced BV2 cells. Furthermore, by utilizing PDTC, an NF-κB antagonist, it was found that the effect of PR was similar to that of PDTC.

Conclusion: PR could hamper inflammation and microglial polarization in 2VO-induced VaD and LPS-induced BV2 cells. Our results showed that PR was a promising Chinese herb to alleviate VaD, and the potential mechanism might be related to NF-κB/NLRP3 signaling pathway.

Objectives: The aim of this study was to develop a clinical application model for the rational use of caffeine.

Background: Caffeine is related to the incidence of neuro immune gastrointestinal diseases. Coffee consumption needs to be optimized in order to reduce the incidence rate.

Purpose: By using KEEG analysis to explore potential molecular signaling pathways involved in the progression of neurological immune gastrointestinal diseases, and analyzing the details of this signaling Pathway using molecular simulation results, which can support AI system for doctor.

Methods: The research team designed a controlled experiment to analyze the differences in reward and reinforcement of Brain pleasure/addiction and dopamine related signaling pathways function between multiple groups of people with different coffee drinking habits and a blank control group. The study team used molecular dynamics methods to investigate the signaling route that links coffee with the binding of dopamine receptor D3.AI is used to predict the prevalence of gastric reflux disease.

Results: Human experiments have shown a correlation between caffeine intake and gastroesophageal reflux disease. AI algorithm results can provide clinical support, and molecular simulation results are consistent with human experimental results. Caffeine and DRD3 protein have a stable interaction system.

Conclusion: The research team elucidated the intermolecular interaction between caffeine and DRD3, and AI algorithms can predict the likelihood of disease occurrence, providing a new strategy for clinical practice. This study has passed ethical approval at Chifeng Cancer Hospital, and the ethical documents for this study have been submitted to the World Health Organization for filing.

Background: Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis- Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (H2O2)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway.

Methods: After preparation of containing serum, the cells were divided into various categories, such as control group, H2O2 group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with H2O2 group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities, and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis.

Results: We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in H2O2-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis.

Conclusion: We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC- 1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).

According to epidemiological studies, diabetes is more common in patients with AD, which suggests that diabetes is a significant risk factor for AD. Accelerating brain cell degeneration, worsening cognitive decline, and increasing susceptibility to AD can be attributed to pathogenic mechanisms linked to diabetes, such as impaired insulin signaling in the brain, neuroinflammation, oxidative stress, mitochondrial dysfunction, and vascular impairment. These factors can also lead to the accumulation of β-amyloid and tau protein phosphorylation. New research suggests that certain drugs used to manage diabetes have different levels of effectiveness in treating or preventing Alzheimer's disease. Exercise has numerous advantages, including the reduction of neuroinflammation, alleviation of oxidative stress and mitochondrial dysfunction, improvement of endothelial and cerebrovascular function, stimulation of neurogenesis, and prevention of pathological changes associated with diabetes-related Alzheimer's disease through various internal mechanisms. This study examined the development of Alzheimer's disease (AD) in relation to diabetes, evaluated the ability of specific antidiabetic drugs to prevent and treat AD, and investigated the impacts and underlying processes of exercise interventions in improving AD treatment for individuals with diabetes.

Background: Gene therapy has been effectively applied in many biological studies and for the treatment of many genetic or cancer diseases. Currently, Recombinant Adeno- Associated Viruses (rAAVs) are one of the main types of delivery vectors used for gene therapy. rAAV vectors produced via the Sf9 cells have the advantages of high rAAV yields, easy scaleup, and low cost.

Method: Here, we used Sf9 rhabdovirus-negative (Sf9-RVN) cells to validate and optimize the rAAV production process, and the fed-batch process increased the rAAV production titre.

Results: In the fed-batch procedure, the cell density reached 12.9×106 cells/mL, which was approximately twice as high as in the batch culture process. The rAAV titre was also approximately 8-fold higher in the fed-batch process, reaching 1.5×1012 VG/mL. The optimized process was validated by generating rAAVs with various serotypes and genes of interest (GOI), all of which gave production titres greater than 1×1012 VG/mL.

Conclusion: We used Sf9-RVN cells to develop a fed-batch rAAV production process that replaces Sf9 cells to meet regulatory standards. This process has good applicability, and the rAAV titre can reach at least 1×1012 VG/mL, which is higher than the level of 1011 VG/mL reported in the literature.

Objective: This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats.

Methods: Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed.

Results: PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman's capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment.

Conclusion: The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, antiglycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Artificial intelligence (AI) is a rapidly transforming drug discovery and development process, significantly impacting the pharmaceutical industry and enhancing human health. This review article examines the tremendous role of AI in analyzing complex biological data, optimizing research processes, and reducing costs of production. Implementation of AI in the pharmaceutical sector can store a vast dataset of manufacturing processes, identify potential disease targets, simulate physiological conditions, and predict drug interactions. The review article also discusses the AI concepts and their applications, particularly in developing solid dosage forms. Advanced algorithms optimize formulation processes, predict pharmacokinetics profiles, and assess drug toxicity profiles, facilitating a more efficient pathway from pilot study to market. Additionally, this review highlights the advancements in 3D printing technologies of dosage forms that have the ability to provide personalized treatment to different individuals. Furthermore, the article explores the opportunities and challenges of AI in healthcare, focusing on applications such as disease diagnosis, digital therapy, and epidemic forecasting. Prominent AI technologies like deep learning and neural networks are examined for their roles in predicting outbreaks of diseases like influenza and COVID-19. As the pharmaceutical landscape evolves, AI is poised to redefine traditional methods. This paves the way for more efficient healthcare solutions. By harnessing the interplay of technology and science, AI not only increases productivity; but it also promotes a new era of precision medicine tailored to the needs of each patient.

Background: Benign prostatic hyperplasia is a non-malignant growth of the prostate gland; it's the most common prostatic growth in aging men. 1,8-cineole is a natural compound that is extracted from the essential oil of several aromatic plants including Eucalyptus spp. Recent studies have demonstrated the anti-inflammatory, antioxidant, and anticancer activities of 1,8-cineole. This study aims to investigate the effects of 1,8-cineole treatment on the development of BPH induced by testosterone in rats.

Method: Thirty adult male rats were divided into three groups (n=10): a control group, an untreated BPH group that received subcutaneous injections of testosterone (3 mg/kg), and a BPH+cineole group that received 50 mg/kg of cineole intraperitoneally in addition to testosterone for 21 days. Histological changes, serum testosterone, and dihydrotestosterone (DHT) levels, prostatic tissue content of the inflammatory biomarkers interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), oxidative stress biomarkers superoxide dismutase (SOD) and malondialdehyde (MDA), angiogenesis biomarker vascular endothelial growth factor (VEGF-A), cellular proliferation biomarker proliferating cell nuclear antigen (PCNA), transforming growth factor beta-1 (TGF-β1), and pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) genes were analyzed.

Results: Cineole treatment led to a reduction in the prostate weight-to-body weight ratio, as well as the restoration of histopathological changes caused by testosterone. Cineole treatment reduced the serum levels of testosterone and DHT, and the prostatic tissue levels of IL-1β, TNF-α, VEGF-A, PCNA, and TGF-β1 compared to those in the BPH group. Additionally, cineole treatment enhanced the SOD activity and decreased the MDA levels in the prostate tissue. Finally, the mRNA expression of the Bax was increased, while the expression of the Bcl-2 was decreased by cineole.

Conclusion: Our results highlight the effectiveness of cineole in preventing BPH development in rats. This preventive effect was attributed to the regulation of inflammatory responses, oxidative stress, cellular proliferation, and apoptosis.