Current pharmaceutical biotechnology最新文献

Introduction: The use of polydeoxyribonucleotide (PDRN) in promoting tissue repair and anti-aging has been hindered by several challenges, including its large molecular weight, susceptibility to decomposition, low bioavailability, and poor stability and skin permeability. Liposome formulation technology has emerged as a promising method in cosmetics, enhancing the penetration and protection of active ingredients.

Method: In this study, a PDRN-loaded nanoliposomal (PDRN-NL) formulation, which exhibited an average particle size of 125 ± 1 nm, a polydispersity index (PDI) of 0.12 ± 0.02, a zeta potential of -52.6 ± 0.8 mV, and an encapsulation efficiency of 81.3%. The stability of the PDRN-NL and its formulations was assessed using the Turbiscan Lab stability analyzer, which predicted a shelf life of up to three years. Furthermore, the in vitro permeability of the PDRN-NL was evaluated using the Franz diffusion cell method.

Results: Results indicated that the cumulative skin permeation of PDRN-NL over 24 hours was 1.22 times higher than that of free PDRN, with skin retention of PDRN-NL being 1.40 times greater. The in vitro release studies demonstrated that liposomal encapsulation not only enhanced permeability but also provided a sustained-release effect and improved stability of PDRN.

Conclusion: Overall, the properties of liposome-encapsulated PDRN were significantly enhanced, presenting a novel solution for the incorporation of PDRN in the development of skincare products.

Background: The traditional Chinese recipe "Erjing Formula", composed of HuangJing and GouQi, is recognized for its tonifying and revitalizing properties, but the active components responsible for these effects are poorly explored. This study investigated the antifatigue effects of Erjing Formula polysaccharides (EJFP).

Methods: Mice were treated with EJFP and subjected to weight-loaded swimming tests. Biochemicals were measured, while muscle changes were analyzed by H&E staining and protein expression by Western blotting.

Objective: The present study aimed to investigate the anti-fatigue effects of EJFP through weight-loaded swimming tests in mice.

Methods: SPF-grade healthy male rat species KM mice were gavaged with EJFP and then subjected to a weight-loaded swimming test. Later, the levels of various biochemical indicators, including blood lactate (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), muscle glycogen (MG), and hepatic glycogen (HG), were measured. The muscle tissue slices were analyzed using hematoxylin and eosin H&E) staining. Additionally, the expression levels of Kelch-like ECH-associated Protein 1 (Keap-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the muscle tissue of each group were detected using Western Blotting.

Results: EJFP (Erjing Formula Polysaccharides) significantly increased swimming time (p ≤ 0.01), reduced oxidative stress markers and detrimental metabolites (BLA, BUN, and MDA), and elevated SOD, MG, and HG levels. Histologically, it improved muscle integrity. Nrf2 expression increased, indicating a relationship between antioxidant effects and antifatigue activity.

Conclusion: EJFP demonstrated anti-fatigue effects, mainly at moderate doses, by modulating the Nrf2/Keap1 pathway and improving glycogen and antioxidant levels. This is the first study to document the anti-fatigue effects of Erjing Formula polysaccharides, establishing a theoretical basis for practical applications in the development of anti-fatigue products.

Aims: The present study aimed to examine the roles of circRNA-circSMAD2 and its regulatory mechanisms in endometriosis (EMs).

Background: Evidence has confirmed that circRNAs play multiple roles in regulating the occurrence and development of EMs, but the regulatory mechanisms of circRNAs in EMs remain largely unknown.

Objective: The roles and regulatory mechanisms of circSMAD2 in EMs.

Method: Eutopic and ectopic endometrium of ovarian EMs as well as normal endometrial tissues, were used to extract circRNA, mRNA, and total proteins. The human endometrial stromal cell lines (ThESCs) and endometrial stromal cells (ESCs) were stimulated with different concentrations or times of 17β-estradiol (E2). The mouse model of EMs was established by implanting uterine horns onto the peritoneum wall using a suture.

Result: Compared with normal tissues, the expression of circSMAD2 was significantly decreased in eutopic and ectopic endometrial tissues. Furthermore, the expression of circSMAD2 was downregulated by E2 in a dose- and time-dependent manner in ThESCs and ESCs. Overexpression of circSMAD2 inhibited the invasion and migration of ThESCs, while knockdown of circSMAD2 exerted the opposite effect. The RNA binding protein quaking (QKI), which is involved in circRNA formation, was lower in eutopic and ectopic endometrial tissues compared to normal tissues.

Conclusion: Moreover, E2 suppressed the expression of circSMAD2 by inhibiting the expression of QKI. Additionally, E2 enabled the expression of estrogen receptor beta (ERβ) to inhibit the expression of QKI and circSMAD2 in vitro and in vivo.

Conclusion: The E2/ERβ/QKI/circSMAD2 pathway was involved in cellular migration and invasion in EMs.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, represent a significant global health challenge with limited therapeutic options. Protein misfolding and aggregation, a common pathological hallmark in these disorders, have emerged as promising targets for therapeutic intervention. Molecular docking techniques have played a pivotal role in the identification and design of small molecules that can modulate protein misfolding, offering new hope for effective treatments. This review provides an overview of recent advancements in molecular docking techniques for targeting protein misfolding in neurodegenerative diseases. We discuss the principles and methodologies behind molecular docking, including various scoring functions and algorithms employed for accurate ligand-protein interactions. Additionally, we explore the use of molecular dynamics simulations and machine learning approaches to enhance the precision of docking studies. Furthermore, we highlight case studies and success stories where molecular docking has contributed to the discovery of potential drug candidates for neurodegenerative diseases. These include compounds that inhibit amyloid-β aggregation in Alzheimer's disease, α-synuclein oligomerisation in Parkinson's disease, and mutant huntingtin aggregation in Huntington's disease. We also discuss the problems and restrictions of molecular docking related to neurodegenerative diseases, such as how to accurately show the flexibility of proteins and why docking results need to be confirmed by experiments. We also discuss the structural biology methods, such as cryo-electron microscopy and X-ray crystallography, and how these techniques might help in improving molecular docking studies.

Objective: The objective of this study is to conduct network toxicology analysis based on smoking habits and develop a simpler and more effective toxicology product ingestion control system.

Background: Smoking behavior can affect the pathogenesis and prognosis of neuroimmune gastrointestinal diseases.

Aims: The purpose of developing tools to assist clinical practice is to avoid the harm of cigarettes to the human body.

Methods: Molecular dynamics method was used to elucidate the biophysical mechanism of TP53 gene mutation caused by harmful ingredients, and the signaling pathway of midbrain edge excitation was determined by molecular dynamics of nicotine and dopamine receptor D3. The possible involvement of nicotine in neuronal damage was determined through the molecular interaction between nicotine and ACHE. Molecular pathways were analyzed based on the aforementioned biological principles, developed artificial intelligence systems and brain computer interface systems.

Results: Several signaling pathways were elucidated, and effective AI algorithms were developed.

Conclusion: The accuracy of artificial intelligence systems is over 70%. This study provides clinical doctors with a new precision medicine strategy and tool to regulate patient behavior and reduce disease risk. Other: This project was approved by the Ethics Committee of Chifeng Cancer Hospital and reported to the WHO.

Background: Antibiofilm agents serve as an essential tool in the fight against antibiotic resistance, and natural products provide a promising source for potential drug leads.

Objective: This study investigates the activity of twenty Bangladeshi medicinal plants against Staphylococcus aureus and Pseudomonas aeruginosa biofilms and predicts the interactions of selected phytochemicals from five of the best performing plants with the active sites of transcriptional regulatory proteins SarA of S. aureus and LasR of P. aeruginosa.

Methods: The plant extracts were tested by microtiter plate-based assay against S. aureus and P. aeruginosa biofilms. Molecular docking and molecular dynamics simulation (MD) were conducted using PyRx and GROMACS, respectively.

Results: The best activity was identified for Cassia fistula and Ananas comosus, showing ≥ 75% inhibition of biofilm formation. ent-Epicatechin-(4α→8)-epiafzelechin (EEE) of C. fistula, cyanidin-3,3',5-tri-O-β-D-glucopyranoside (CTG) of A. comosus, and 7-O-(4-hydroxy-Ecinnamoyl)- spinoside of A. spinosus showed the best predictive binding affinity (-7.6, -7.6 and - 7.7 kcal/mol, respectively) for SarA. EEE was the only ligand to exhibit a stable ligand-protein complex with SarA in the MD simulation of 200 ns (binding energy of MMPBSA analysis - 39.899 kJ/mol). Chrysophanol, epicatechin and physcion, of C. fistula (-10.5, -10.5, and -11.0 kcal/mol, respectively) and auraptene of F. limonia (-10.8 kcal/mol) showed the best predictive binding affinity for LasR. Epicatechin showed the most stable ligand-protein complex with LasR (binding energy of MMPBSA analysis -63.717 kJ/mol).

Conclusion: Epicatechin and its derivative EEE could be used as scaffolds for the d evelopment of new antibiofilm agents against P. aeruginosa and S. aureus, respectively.

Introduction: Pain, infection, and dry socket are the primary complications following tooth extraction. Hence, the aim of this study was to evaluate the pain range and incidence of dry socket after using a hemostatic spongy material containing aloe vera nanoparticles after split-mouth extraction of the mandibular first and second molars, compared to a control sponge without aloe vera nanoparticles in patients referred to the Tabriz Faculty of Dentistry.

Materials and methods: This double-blind, split-mouth clinical study was conducted on 30 patients referred to the Faculty of Dentistry in Tabriz. Patients were selected according to specific inclusion and exclusion criteria and required extraction of two teeth. After tooth extraction, an aloe vera nanoparticle-containing hemostatic sponge was randomly placed in one extraction site, while a sponge without aloe vera nanoparticles served as the control in the other extraction site. Pain levels were measured at 12, 24, 48, and 72 h after extraction using a Visual Analog Scale (VAS), where patients marked their pain level from 1 (lowest pain) to 10 (highest pain) at each time point. Patients received a form to record the required information and instructions on how to do so, which they submitted upon completion. To assess the occurrence of dry socket, patients were asked to come four days after extraction. Data were analyzed using SPSS software with relevant statistical tests, considering a significance level of P<0.05.

Results: In both groups, the average pain levels decreased significantly over 72 h (P=0.001 and P=0.01 for the test and control groups, respectively). Additionally, for 48 h and 72 h time points, the test group showed better pain control results than the control group (P=0.04 and P=0.04 for 48 h and 72 h, respectively). No cases of dry sockets were found in either group.

Conclusion: The aloe vera-containing sponge demonstrated better performance in pain control following tooth extraction compared to the control group. For dry socket occurrence, both sponges showed similar results.

COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that is one of the most significant challenges to public health over the past few years. Most people are vulnerable to SARS-CoV-2, but older adults are more vulnerable. Aging is one of the major risk factors for the detrimental consequences of COVID-19, likely due to chronic inflammation and immunosenescence, both of which are the characteristics of old age. Immunosenescence refers to the weakening of the immune system with age while inflammaging describes the low-grade chronic inflammation seen in older individuals. One key aspect of human aging is immune deficiency. During aging, our body's defense system weakens, resulting in decreased responses to infection by novel pathogens and a reduced ability to become immunized. The presence of chronic inflammation and viral infection in old age may cause several adverse unpredictable outcomes increasing the propensity and severity of the disease and requires to be considered, enabling people to better prepare for the potential consequences of this ongoing pandemic. This requires consideration so that individuals can better be prepared to address the potential consequences of this ongoing pandemic. In this review, we discuss the clinical characteristics of elderly COVID-19 patients and survey the associated molecular pathways that are pivotal for the interactions of the coronavirus and host cellular responses, including immunosenescence, inflammation, telomere attrition, impaired autophagy, mitochondrial dysfunction and alterations in major aging signaling pathways, which are crucial for the discovery of new therapeutic and preventive methods in the ongoing pandemic.

Neurological illnesses encompass a broad spectrum of conditions that affect the brain, spine, and nerves, often impairing daily functioning. The global prevalence of these illnesses is rising, posing significant health challenges. This study investigates the beneficial effects of probiotics and postbiotics in managing various neurological disorders, providing a comprehensive analysis of their use in treating these conditions. The article explores innovative, holistic approaches to neurological care, emphasizing patient-centered therapeutic interventions. Compelling evidence suggests that probiotics and postbiotics positively impact several neurological diseases. Specifically, the findings indicate that these treatments can modulate the gut-brain axis, reduce neuroinflammation, and enhance neuronal protection. The study highlights the potential of specific bacteria and their byproducts to ameliorate neurological disorders. Despite promising results, the current data underscore the challenges in future research on the therapeutic benefits of probiotics and postbiotics for neurological illnesses and underscores the critical role of the gut-brain connection and the microbiome in maintaining neurological health. It also examines the safety and feasibility of using probiotics and postbiotics as adjunct therapies, delving into the mechanisms underlying their beneficial effects. Probiotics and postbiotics demonstrate a capacity to enhance the regenerative potential of the human brain, and recent evaluations provide additional evidence supporting their efficacy and safety. However, further rigorous clinical trials are necessary to validate these findings and establish the most effective therapeutic strategies for treating neurological disorders.

Aims: To identify potential phytochemical-based drugs for both wild-type and Omicron variants of SARS-CoV-2 using virtual screening and molecular dynamic simulation.

Background: Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by SARS-CoV-2. Since 2019, multiple variants have been reported from all over the world and the emergence of new variants of SARS-CoV-2 is a major concern.

Objective: To identify potential phytochemicals that can be used as drugs against different variants of SARS-CoV-2.

Methods: In our present study, we have selected 594 phytochemicals and performed virtual screening to identify potential drug candidates. The screening commenced with molecular docking techniques with both ACE2 (Human) and Spike protein (wild-type and Omicron variant), followed by prediction of pharmacokinetics parameters and toxicity. The Schrodinger tools, Swiss ADME, and ProTox-II accomplish the analysis. Further, molecular dynamics simulation, binding free energy calculation and meta-dynamics study was performed for best protein-ligand complexes of both proteins using GROMACS and gmx_MMPBSA to validate the stability of the docked complexes.

Results: we have identified 6 and 4 drugs as spike protein inhibitors for wild-type and Omicron variants, respectively. 6 drugs were identified as ACE2 receptor inhibitors. We have identified silymarin as a common drug inhibitor for both pathogen (Wild-type, and Omicrons spikes) as well as host (human ACE2) protein that reflects its ability to inhibit the host-pathogen interaction and prevent infection.

Conclusion: We have found some potential Phytochemicals that can be used against different variants of SARS-CoV-2 such as silymarin.