Current Pharmaceutical Biotechnology - Online First

Psoriasis is a chronic skin disease that affects patients' quality of life. Treating psoriasis remains a significant challenge due to various factors, including individual response variability, drug resistance, and the range of side effects associated with currently available medications. Nowadays, numerous research efforts are being made aiming at overcoming the obstacles of the available psoriasis treatments are still taking place.

This research aims to develop and evaluate a nanogel formulation loaded with khellin for the effective treatment of psoriasis.

Khellin nanogel was prepared using the self-assembly method with a synthesized gelatin-pluronic copolymer. The novel formulation was characterized via size, size distribution, encapsulation efficiency, in vitro release, and ex vivo skin deposition.

The final nanogel formulation had an average size of 119.6 nm, a polydispersity index of 0.248 and an excellent encapsulation efficiency of 88%. In vitro drug release study demonstrated that nanogels showed a great accelerated drug release profile by releasing khellin within 2 hours, which is suitable for photochemotherapy applications. In addition, khellin-loaded nanogel formulation had 1.7 times better skin deposition potential than the control gel formulation.

The prepared nanogel formulation provides a high potential to be an ideal drug delivery system of khellin in combination with phototherapy for more efficient psoriasis treatment.

To predict and assist in the treatment of colorectal cancer.

Precision medicine systems can provide strategy optimization for the diagnosis and treatment of colorectal cancer to meet the needs of clinical pricing institutions.

To design an artificial intelligence multimodal gastrointestinal disease clinical information system based on neuroimmune gene regulation.

The system includes the use of cell gene expression levels to predict the 5-year survival rate of cancer patients, and the development of disease incidence rate prediction models based on immune cell status and living habits in somatic cell testing. The biological mechanism of feature selection in survival prediction systems was elucidated using single-cell sequencing technology, and this mechanism was analyzed in depth using molecular simulation techniques. Based on NCAM1 and CADM1 genes, biological activation pathway analysis was conducted to explore the biological mechanism of their synergistic immune genome regulation of gastrointestinal tumor proliferation.

The accuracy of each model is higher than 0.70. The experimental credibility is high.

The research team conducted a detailed analysis of the biological characteristics of AI algorithms and reached a consensus with clinical experts. The ethical approval number of Chifeng Cancer Hospital is 202401, which has been reported by the World Health Organization.

Given the high mortality associated with Cirrhotic Portal Hypertension (CPH) worldwide, this study investigates the mechanism by which baicalin (BA), known for its beneficial effects on cirrhosis, alleviates CPH.

The CPH model was established in Sprague-Dawley (SD) rats, followed by 4-week oral administration of 30 and 60 mg/kg/day BA. SD rats were randomly assigned to four groups (n=6/group): Con, Model, BA-30, and BA-60. Portal vein smooth muscle cells (PVSMCs, extracted from SD rats, n=6) were incubated with 5, 10 and 20 μmol/L BA. The levels of liver function indicators and von Willebrand factor (vWF) were determined by biochemical and immunohistochemical analyses, respectively. The portal pressure (PP) was examined. The liver fibrosis was detected by Sirius red staining. The levels of fibrosis-, angiogenesis- and proliferation-related indicators, zinc fingers and homeoboxes 2 (ZHX2), and matrix metallopeptidase 14 (MMP14) were quantified by Western blot. The levels of and interaction between ZHX2 and MMP14 were separately measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The proliferation and migration of PVSMCs were assessed by EdU staining and scratch test, respectively.

BA up-regulated ZHX2 and down-regulated MMP14 (P<0.001). BA concentration-dependently suppressed liver fibrosis, PP, and angiogenesis in the liver tissue, as well as PVSMC proliferation and migration, while enhancing liver function (P<0.05). Further, according to the GRNdb database and luciferase reporter assay, ZHX2 is bound with the promoter of MMP14. ZHX2 could suppress the MMP14 level (P<0.001). ZHX2 silencing reversed the effects of BA treatment on the proliferation and migration of PVSMCs, whereas MMP14 silencing could further offset the role of ZHX2 silencing in the BA-treated PVSMCs (P<0.05).

BA up-regulates ZHX2 to reduce the level of MMP14 and alleviate CPH. Understanding the mechanisms of BA in CPH may provide a foundation for novel interventions to attenuate CPH.

Selenium is an important trace element that plays crucial roles in metabolism, immune function, and antioxidant defense. As an antioxidant, selenium helps to alleviate postpartum uterine inflammation and promotes uterine recovery. However, the exact mechanism underlying the role of selenium in postpartum uterine recovery is not fully understood.

This study aimed to identify the underlying mechanism and examine how selenium enhances postpartum uterine healing.

Female ICR mice aged 8 weeks were classified into five groups: control, postpartum model, low-dose selenium (100 nm), medium-dose selenium (200 nm), and high-dose selenium (400 nm). Endometrial morphology was evaluated by hematoxylin and eosin (H&E) staining. Oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA), and inflammatory factors, including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), were measured using commercially available kits. GPX1, GPX4, and nuclear factor erythroid 2-related factor 2 (NRF2) expression were determined using real-time PCR and WB.

We found damage and bleeding points in the endometrium and destruction of the ultrastructure of endometrial cells in the postpartum model group; however, mice treated with a high dose (400 nm) of selenium showed alleviated levels of pathological alteration in the endometrium. In addition, the levels of MDA in the postpartum mice group increased, while the SOD, CAT, and GPX levels decreased; however, changes in these oxidative stress markers were reversed after selenium treatment. For inflammatory factors, high levels of TNF-α and IL-1β were observed in postpartum mice, whereas they were decreased in selenium-treated groups. GPX1, GPX4, and NRF2 expression were reduced in postpartum model mice, but upregulated in selenium-treated mice.

Selenium supplementation ameliorated postpartum uterine oxidative stress and inflammation and promoted uterine recovery via the GPX1/GPX4/NRF2 pathway in mice.

Overdose involving opioids is the black heart of the addiction crisis. “Pre-addiction,” as an encouraging concept by NIDA and NIAAA, seems best captured with the construct of dopamine dysregulation. Referring to the abundant publications on “Reward Deficiency Syndrome” (RDS), Genetic Addiction Risk Score (GARS) test, RDSQ29, and KB220, Pre-addiction can be referred to as “reward dysregulation” as a suitable suggestion. The hypothesis is that the true phenotype is RDS, and other behavioral disorders are endophenotypes where the genetic variants play important roles, specifically in the Brain Reward Cascade (BRC).

This study tested the pharmacogenomics of the GARS panel by a multi-model in silico investigation in four layers: 1) Protein-Protein Interactions (PPIs); 2) Gene Regulatory Networks (GRNs); 3) Disease, drugs and chemicals (DDCs); and 4) Gene Coexpression Networks (GCNs).

All in silico findings were combined in an Enrichment Analysis for 59 refined genes, which represented highly significant associations of dopamine pathways in the BRC and supported our hypothesis.

This paper provides scientific evidence for the importance of incorporating GARS as a predictive test to identify Pre-addiction, introduce unique therapeutic targets assisting in the treatment of pain, drug dosing of prescription pharmaceuticals, and identify the risk for subsequent addiction early in -life.

The purpose of the present research was to assess the protective role of coffee in thioacetamide-induced nephrotoxicity.

The experimental period consisted of 18 weeks, divided into two phases. Four experimental groups were designed, each consisting of six rats. Group I was considered an untreated control group. Groups II and III were intraperitoneally injected with thioacetamide at a dose of 200 mg/kg body weight twice a week for twelve weeks during the first phase of the study. In the second phase, group II received saline, and group III and group IV received 0.4 mg/Kg of coffee daily for six weeks. The biochemical analysis was evaluated by the estimation of plasma urea, uric acid, creatinine, Malondialdehyde (MDA), Superoxide Dismutase (SOD), and catalase.

Thiocetamide-induced nephrotoxicity resulted in the reduction of body weight, superoxide dismutase, and catalase activities, and an increase in kidney weight, plasma urea, uric acid, creatinine, and tissue malondialdehyde. Supplementation with coffee effectively increased body weight while reducing elevated levels of urea, uric acid, creatinine, and MDA. It also restored SOD and catalase activities in Group III (TAA + Coffee-treated).

This work shows that coffee can protect the kidneys against thioacetamide-induced nephrotoxicity in a rat model. It highlights the antioxidant potential of coffee by its ability to restore enzymatic antioxidant activity (SOD and catalase), lower oxidative stress markers (MDA), and enhance renal function measures (urea, creatinine, and uric acid). The study fills a significant gap by demonstrating coffee as a viable natural therapeutic agent for oxidative stress-induced kidney impairment, providing an alternative to conventional treatments with fewer side effects.

Diabetic Kidney Disease (DKD) is a major cause of End-Stage Renal Disease (ESRD) and lacks effective treatments. Tangmaikang Granules (TMK), a multi-herb traditional Chinese medicine formulation, have shown potential in managing DKD. However, the precise active components, molecular mechanisms, and therapeutic advantages of TMK remain unclear.

This study tests the hypothesis that TMK granules exert protective effects on DKD by targeting multiple pathways involved in oxidative stress, inflammation, and apoptosis in podocytes through a multi-targeted approach. The aim was to identify TMK’s bioactive components, evaluate its therapeutic potential, and uncover its molecular mechanisms in DKD.

The bioactive constituents in TMK were determined through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Drug targets were identified using SwissTargetPrediction and SuperPred, whereas DKD-associated targets were obtained from the GeneCards, DisGeNET, OMIM, and TTD databases. A Protein-Protein Interaction (PPI) network was constructed, and key targets were identified via topological analysis. Molecular docking and dynamics simulations were performed to evaluate stable binding interactions. GO and KEGG pathway enrichment analyses were conducted to uncover relevant signaling pathways. TMK's effects on oxidative stress, inflammation, and apoptosis in podocytes were assessed using CCK-8, flow cytometry, RT-qPCR, ELISA, and Western blot assays.

Thirty active compounds and 384 potential therapeutic targets were identified, with eight key targets. Pathway enrichment analysis revealed TMK’s involvement in AGE-RAGE, EGFR, HIF-1, and apoptosis pathways, affecting inflammatory cytokine responses and oxidative stress. In vitro experiments demonstrated that TMK significantly reduced oxidative stress, inflammation, and apoptosis in podocytes by inhibiting the MAPK and NF-κB pathways.

TMK granules target DKD through a multi-component, multi-target strategy, effectively mitigating oxidative stress and suppressing inflammatory and apoptotic pathways. This study integrates advanced computational and experimental methods, demonstrating TMK’s unique therapeutic potential and providing a robust foundation for its clinical application in DKD management.