Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer.

Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane's Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies.

Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

Efficient catalyst-free N2 fixation by water radical cations under ambient conditions.

The growth and sustainable development of humanity is heavily dependent upon molecular nitrogen (N2) fixation. Herein we discover ambient catalyst-free disproportionation of N2 by water plasma which occurs via the distinctive HONH-HNOH+• intermediate to yield economically valuable nitroxyl (HNO) and hydroxylamine (NH2OH) products. Calculations suggest that the reaction is prompted by the coordination of electronically excited N2 with water dimer radical cation, (H2O)2+•, in its two-center-three-electron configuration. The reaction products are collected in a 76-needle array discharge reactor with product yields of 1.14 µg cm-2 h-1 for NH2OH and 0.37 µg cm-2 h-1 for HNO. Potential applications of these compounds are demonstrated to make ammonia (for NH2OH), as well as to chemically react and convert cysteine, and serve as a neuroprotective agent (for HNO). The conversion of N2 into HNO and NH2OH by water plasma could offer great profitability and reduction of polluting emissions, thus giving an entirely look and perspectives to the problem of green N2 fixation.

The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

A comprehensive study of Ephedra sinica Stapf-Schisandra chinensis (Turcz.) Baill herb pair on airway protection in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedra sinica Stapf (Mahuang) and Schisandra chinensis (Turcz.) Baill (Wuweizi) are commonly utilized in traditional Chinese medicine for the treatment of cough and asthma. The synergistic effect of Mahuang-Wuweizi herb pair enhances their efficacy in alleviating respiratory symptoms, making them extensively employed in the management of respiratory disorders. Although previous studies have demonstrated the therapeutic potential of Mahuang-Wuweizi in pulmonary fibrosis, the precise mechanism underlying their effectiveness against asthma remains elusive. AIM OF THE STUDY: The objective of this study is to investigate the mechanism underlying the preventive and therapeutic effects of Mahuang-Wuweizi herb pair on asthma progression, focusing on airway inflammation and airway remodeling. MATERIALS AND METHODS: The active constituents and potential mechanisms of Mahuang-Wuweizi in the management of asthma were elucidated through network pharmacology analysis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to detect the main components of Mahuang-Wuweizi decoction. A rat model of bronchial asthma was established, and the effects of Mahuang-Wuweizi were investigated using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) staining, enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The results of network pharmacological prediction showed that Mahuang had 22 active components and Wuweizi had 8 active components, with 225 potential targets. 1159 targets associated with asthma and 115 targets that overlap between drugs and diseases were identified. These include interleukin-6 (IL-6), tumor necrosis factor (TNF), Tumor Protein 53, interleukin-1ß (IL-1ß), as well as other essential targets. Additionally, there is a potential correlation between asthma and Phosphatidylinositol 3 kinase (PI3K)/Protein Kinase B (AKT) signaling pathway, calcium ion channels, nuclear factor-kappa B (NF-κB) signaling pathway, and other signaling pathways. The animal experiment results demonstrated that treatment with Mahuang and Wuweizi, in comparison to the model group, exhibited improvements in lung tissue pathological injury, reduction in collagen fiber accumulation around the airway and proliferation of airway smooth muscle, decrease in concentration levels of IL-6, TNF-α and IL-1ß in lung tissue, as well as alleviation of airway inflammation. Furthermore, Mahuang and Wuweizi suppressed the expression of phospholipase C (PLC), transient receptor potential channel 1 (TRPC1), myosin light chain kinase (MLCK), NF-κB P65 protein in ovalbumin (OVA)-sensitized rat lung tissue and downregulated the mRNA expression of PLC, TRPC1, PI3K, AKT, NF-κB P65 in asthmatic rats. These findings were consistent with network pharmacological analysis. CONCLUSION: The results show that the synergistic interaction between Mahuang and Wuweizi occur, and they can effectively reduce airway remodeling and airway inflammation induced by inhaling OVA in bronchial asthma rats by inhibiting the expression of PLC/TRPC1/PI3K/AKT/NF-κB signaling pathway. Therefore, Mahuang and Wuweizi may be potential drugs to treat asthma.

Pueraria thomsonii Radix Water Extract Alleviate Type 2 Diabetes Mellitus in db/db Mice through Comprehensive Regulation of Metabolism and Gut Microbiota.

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, rich polyphenols and polysaccharides from Pueraria Thomsonii Radix water extract (PTR) were quantitatively determined, and then the effects of PTR on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could alleviate pancreatic tissue damage, significantly decrease fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), urinary glucose (UGLU), and urinary albumin/creatinine ratio (UACR). Metabolomics showed that the Diabetes Control (DM) group produced 109 differential metabolites, of which 74 could be regulated by PTR. In addition, 16S rRNA sequencing was performed in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes(F/B) ratio and regulate three beneficial bacteria and one harmful bacterium. In conclusion, the results showed that PTR could ameliorate the T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric acid (GABA) may be involved in the regulation of the microbiota-gut-brain axis (MGB) and thus affects the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Protective effects of lycopene against zearalenone-induced reproductive toxicity in early pregnancy through anti-inflammatory, antioxidant and anti-apoptotic effects.

Zearalenone is a mycotoxin that is widely present in feed and raw materials and can cause severe reproductive toxicity. Lycopene is a natural carotenoid with antioxidant and anti-inflammatory pharmacological effects, but the protective effects of lycopene against zearalenone-induced uterine damage have not been reported. The aim of this study was to investigate the protective effect of lycopene treatment in early pregnancy on zearalenone-induced uterine damage and pregnancy impairment and its mechanism. Reproductive toxicity was induced by consecutive gavages of zearalenone at 5 mg/kg body weight during gestational days (GDs) 0-10 and in the presence or absence of oral administration of lycopene (20 mg/kg BW). The results showed that lycopene may alleviate zearalenone-induced pathological uterine histological damage and disturbances in oestradiol (E2), follicle-stimulating hormone (FSH), progesterone (P) and luteinizing hormone (LH) secretion. Lycopene increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) production, providing protection against zearalenone-induced oxidative stress in the uterus. Additionally, lycopene significantly reduced levels of pro-inflammatory cytokines, including interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and elevated levels of the anti-inflammatory factor interleukin 10 (IL-10), inhibiting the zearalenone-induced inflammatory response. In addition, lycopene improved the homeostasis of uterine cell proliferation and death via the mitochondrial apoptosis pathway. These data provide strong evidence that lycopene can be further developed into a potential new drug for the prevention or treatment of zearalenone-induced reproductive toxicity.

Use of Carbon Nanoparticles to Improve the Efficiency of Harvesting Lymph Nodes in Rectal Cancer.

BACKGROUND: The accurate determination of lymph node status in patients with rectal cancer requires harvesting a certain number of lymph nodes. This study investigated whether using carbon nanoparticles (CNs) could improve the efficiency of harvesting lymph nodes in rectal cancer patients. MATERIALS AND METHODS: Data from patients with rectal cancer treated with radical resection were collected from Nanfang Hospital between January 2014 and June 2021. Patients in the CN group received a CN suspension 1 day before surgery, which was endoscopically injected around the tumor. A 1:1 case-matched study was performed using the propensity score. The efficiency of harvesting lymph nodes was investigated by comparing the number of total nodes, total time, and percentage of nodes <5 mm in size between the CN and non-CN groups. RESULTS: A total of 768 patients were included, with 246 patients who underwent CN injection and 522 patients who did not. After matching, 246 pairs of patients were analyzed. After matching, the number of total nodes of each sample was significantly higher in the CN group than in the non-CN group ( P <0.001). The total time for node detection ( P <0.001) was significantly shorter in the CN group. The percentage of nodes <5 mm in size was increased significantly in the CN group ( P <0.001). Among patients with clinical staging I/II, the difference in positive LNs was significant (21.79% vs. 11.95%, P =0.029). CONCLUSIONS: The application of CNs improved the efficiency of harvesting lymph nodes during rectal cancer surgery.

Development and validation of a collagen signature to predict the prognosis of patients with stage II/III colorectal cancer.

The tumor, nodes and metastasis (TNM) classification system provides useful but incomplete prognostic information and lacks the assessment of the tumor microenvironment (TME). Collagen, the main component of the TME extracellular matrix, plays a nonnegligible role in tumor invasion and metastasis. In this cohort study, we aimed to develop and validate a TME collagen signature (CSTME) for prognostic prediction of stage II/III colorectal cancer (CRC) and to compare the prognostic values of "TNM stage + CSTME" with that of TNM stage alone. Results indicated that the CSTME was an independent prognostic risk factor for stage II/III CRC (hazard ratio: 2.939, 95% CI: 2.180-3.962, p < 0.0001), and the integration of the TNM stage and CSTME had a better prognostic value than that of the TNM stage alone (AUC(TNM+CSTME) = 0.772, AUC TNM = 0.687, p < 0.0001). This study provided an application of "seed and soil" strategy for prognosis prediction and individualized therapy.

[Modern research progress in external application of traditional Chinese medicine to acupoints].

Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.

The preparation, characterization, and application of porous core-shell composite particles produced with laboratory-scale spray dryer.

OBJECTIVE: To prepare porous core-shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. SIGNIFICANCE: The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. RESULTS: (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10-25% when compared with CPs tablets; (iv) The values of Carr's index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. CONCLUSIONS: The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.

Study of Hydroxypropyl ß-Cyclodextrin and Puerarin Inclusion Complexes Encapsulated in Sodium Alginate-Grafted 2-Acrylamido-2-Methyl-1-Propane Sulfonic Acid Hydrogels for Oral Controlled Drug Delivery.

Puerarin has been reported to have anti-inflammatory, antioxidant, immunity enhancement, neuroprotective, cardioprotective, antitumor, and antimicrobial effects. However, due to its poor pharmacokinetic profile (low oral bioavailability, rapid systemic clearance, and short half-life) and physicochemical properties (e.g., low aqueous solubility and poor stability) its therapeutic efficacy is limited. The hydrophobic nature of puerarin makes it difficult to load into hydrogels. Hence, hydroxypropyl-ß-cyclodextrin (HP-ßCD)-puerarin inclusion complexes (PIC) were first prepared to enhance solubility and stability; then, they were incorporated into sodium alginate-grafted 2-acrylamido-2-methyl-1-propane sulfonic acid (SA-g-AMPS) hydrogels for controlled drug release in order to increase bioavailability. The puerarin inclusion complexes and hydrogels were evaluated via FTIR, TGA, SEM, XRD, and DSC. Swelling ratio and drug release were both highest at pH 1.2 (36.38% swelling ratio and 86.17% drug release) versus pH 7.4 (27.50% swelling ratio and 73.25% drug release) after 48 h. The hydrogels exhibited high porosity (85%) and biodegradability (10% in 1 week in phosphate buffer saline). In addition, the in vitro antioxidative activity (DPPH (71%), ABTS (75%), and antibacterial activity (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) indicated the puerarin inclusion complex-loaded hydrogels had antioxidative and antibacterial capabilities. This study provides a basis for the successful encapsulation of hydrophobic drugs inside hydrogels for controlled drug release and other purposes.

Astilbin Attenuates Cadmium-Induced Adipose Tissue Damage by Inhibiting NF-κB Pathways and Regulating the Expression of HSPs in Chicken.

Cadmium (Cd) can damage tissues by inducing oxidative stress, lymphocyte infiltration, and inflammation in these sites. Meanwhile, astilbin (Ast) is an antioxidant agent. At present, only a few mechanisms of Cd-induced adipose tissue damage have been described. Herein, we assessed the potential protective effects and the molecular mechanism underlying the antioxidant properly of Ast after Cd intake in chicken adipose tissue. In this study, a total of 160 7-day-old roosters were randomly divided into four groups. Roosters were fed with a basic diet (C group), Ast 40 mg/kg (Ast group), CdCl2 150 mg/kg + Ast 40 mg/kg (Cd/Ast group), and CdCl2 150 mg/kg (Cd group) for 60 days. We found that Cd intake changed the morphology and structure of adipose tissues and decreased the expression of several antioxidants, including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), but increased those of oxidative stress markers including malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), NO, and H2O2. Cd further activated the nuclear factor kappa B (NF-κB) signaling pathway and increased the expression of the inflammation-related mediators, interleukin 1beta (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), cyclooxygenase-2 (COX-2), iNOS, prostaglandin E synthase (PTGES), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Cd-induced oxidative stress upregulated the expression of three heat shock proteins (HSPs), including HSP27, HSP70, and HSP90. Summarily, Cd causes oxidative stress-mediated tissue damage by activating the NF-κB pathway, promoting inflammation and upregulating the expression of HSPs. However, Ast supplementation modulates oxidative stress in adipose tissue by inhibiting inflammation mediated by the NF-κB pathway and regulating the expression of HSPs.

Exploring the mechanism of the antithrombotic effects of Pueraria lobata and Pueraria lobata var. thomsonii based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. thomsonii (Benth.) Maesen are nutritious medicine food homology plants that are widely used in the food and health products industry and are excellent natural materials for the development of new health foods, with great potential for domestic and foreign markets. Clinically, P. lobata and P. thomsonii are used to treat coronary heart disease, atherosclerosis, cerebral infarction and other cardiovascular diseases, and antithrombotic actions may be their core effect in the treatment of thrombotic diseases. However, the underlying mechanisms of the antithrombotic properties of P. lobata and P. thomsonii have not been clarified. METHODS: First, P. lobata and P. thomsonii were identified by high-performance liquid chromatography (HPLC). An arteriovenous bypass thrombosis rat model was established. Thrombus dry‒wet weight, platelet accumulation rate and the four coagulation indices, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB), were detected in plasma to manifest the P. lobata and P. thomsonii antithrombotic function. Network pharmacology and molecular docking methods were used to obtain key targets and verify reliability. David 6.8 was used for GO and KEGG analyses to explore pathways and potential targets for P. lobata and P. thomsonii antithrombotic functions. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2), cyclooxygenase 2 (COX-2), myeloperoxidase (MPO) and endothelial nitric oxide synthase (eNOS) were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that P. lobata and P. thomsonii can reduce thrombus dry‒wet weight and platelet accumulation in rats and inhibit TT, APTT, FIB, and PT. A comprehensive network pharmacology approach successfully identified 9 active ingredients in P. lobata and P. thomsonii. The main active ingredients include polyphenols, amino acids and flavonoids. A total of 15 antithrombotic function targets were obtained, including 3 key targets (PTGS2, NOS3, MPO). Pathway analysis showed 10 significant related pathways and 29 biological processes. P. lobata and P. thomsonii inhibited platelet aggregation by upregulating PGI2 and downregulating TXA2, inhibited PTGS2 to reduce inflammation, and increased the level of eNOS to promote vasodilation. In addition, P. lobata and P. thomsonii alleviated oxidative stress by increasing SOD levels and significantly decreasing MDA contents. CONCLUSION: The results of the study further clarify the antithrombotic mechanism of action of P. lobata and P. thomsonii, which provides a scientific basis for the development of new drugs for thrombogenic diseases and lays the foundation for the development of P. lobata and P. thomsonii herbal resources and P. lobata and P. thomsonii health products.

JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK - Anaplastic Large Cell Lymphomas : New Insights into Their Heterogeneity.

Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a group of heterogenous CD30 + T-cell non-Hodgkin lymphomas. Previous studies have highlighted the importance of JAK/STAT3 signaling activation in the molecular pathogenesis of ALK - ALCLs. In the present study, we aimed to establish a potential relationship between JAK/STAT3 signaling activation and clinicopathologic features in ALK - ALCLs, and further recognize the heterogenous nature of these neoplasms. Immunohistochemistry staining of the phosphorylated-STAT3 (p-STAT3) and dual-specificity protein phosphatase 22 ( DUSP22 ) gene rearrangement analysis were performed. Forty-five cases of ALK - ALCL were divided into 3 groups, including 9 DUSP22 -rearranged ALCLs, 21 p-STAT3 + double-negative (DN) ALCLs (both ALK and DUSP22 rearrangement negative), and 15 p-STAT3 - DN-ALCLs. Morphologically, p-STAT3 + DN-ALCLs exhibited sheet-like neoplastic cells and sometimes showed large pleomorphic cells scattered in a lymphocyte-rich background more frequently than those in other ALK - ALCLs subtypes. Phenotypically, the p-STAT3 + DN-ALCLs frequently expressed cytotoxic molecules, epithelial membrane antigen, and programmed death-ligand 1, whereas CD3 and CD5 expression was not observed. Clinically, patients with p-STAT3 + DN-ALCLs had a better prognosis than those with p-STAT3 - DN-ALCLs. These observations suggest that p-STAT3 + DN-ALCLs represent a distinct subtype of ALK - ALCLs. Identifying ALK - ALCL subtypes by using p-STAT3 staining and DUSP22 rearrangement is a promising approach that may contribute to risk stratification and better treatment decisions in the future clinical practice.

Natural Products as Anticancer Agents: Current Status and Future Perspectives.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.

Gallic Acid-Loaded Sodium Alginate-Based (Polyvinyl Alcohol-Co-Acrylic Acid) Hydrogel Membranes for Cutaneous Wound Healing: Synthesis and Characterization.

Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop a hydrogel membrane comprised of sodium alginate, polyvinyl alcohol, acrylic acid, and gallic acid for treating skin wounds. The newly developed membranes were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), sol-gel fraction, porosity, mechanical strength, swelling, drug release and data modelling, polymeric network parameters, biodegradation, and antioxidation (DPPH and ABTS) and antimicrobial activity against Gram-positive and negative bacteria. The results revealed that hydrogel membranes were crosslinked successfully and had excellent thermal stability, high drug loading, greater mechanical strength, and exhibited excellent biodegradation. Additionally, the swelling ability and the porosity of the surface facilitated a controlled release of the encapsulated drug (gallic acid), with 70.34% release observed at pH 1.2, 70.10% at pH 5.5 (normal skin pH), and 86.24% at pH 7.4 (wounds pH) in 48 h. The gallic acid-loaded hydrogel membranes showed a greater area of inhibition against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli bacteria as well as demonstrated excellent antioxidant properties. Based on Franz cell analyses, the permeation flux of the drug from optimized formulations through mice skin was 92 (pH 5.5) and 110 (pH 7.4) µg/cm2·h-1. Moreover, hydrogel membranes retained significant amounts of drug in the skin for 24 h, such as 2371 (pH 5.5) and 3300 µg/cm2 (pH 7.4). Acute dermal irritation tests in rats showed that hydrogel membranes were nonirritating. Hydrogel membranes containing gallic acid could be an effective option for improving wound healing and could result in faster wound healing.

Synthesis of Gallic Acid-Loaded Chitosan-Grafted-2-Acrylamido-2-Methylpropane Sulfonic Acid Hydrogels for Oral Controlled Drug Delivery: In Vitro Biodegradation, Antioxidant, and Antibacterial Effects.

In this study, chitosan (CS) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS)-based hydrogels were formulated by the free radical polymerization technique for the controlled release of gallic acid. Fourier transform infrared spectroscopy (FTIR) confirmed the successful preparation and loading of gallic acid within the hydrogel network. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the increased thermal stability of the hydrogels following the crosslinking and polymerization of chitosan and AMPS. In X-ray diffraction analysis (XRD), the crystallinity of the raw materials decreased, indicating strong crosslinking of the reagents and the formation of a new polymeric network of hydrogels. Scanning electron microscopy (SEM) revealed that the hydrogel had a rough, dense, and porous surface, which is consistent with the highly polymerized composition of the hydrogel. After 48 h, the hydrogels exhibited higher swelling at pH 1.2 (swelling ratio of 19.93%) than at pH 7.4 (swelling ratio of 15.65%). The drug release was analyzed using ultraviolet-visible (UV-Vis) spectrophotometer and demonstrated that after 48 h, gallic acid release was maximum at pH 1.2 (85.27%) compared to pH 7.4 (75.19%). The percent porosity (78.36%) and drug loading increased with the increasing concentration of chitosan and AMPS, while a decrease was observed with the increasing concentration of ethylene glycol dimethyl methacrylate (EGDMA). Crosslinking of the hydrogels increased with concentrations of chitosan and EGDMA but decreased with AMPS. In vitro studies demonstrated that the developed hydrogels were biodegradable (8.6% degradation/week) and had antimicrobial (zone of inhibition of 21 and 16 mm against Gram-positive bacteria Escherichia coli and Staphylococcus aureus as well as 13 mm against Gram-negative bacteria Pseudomonas aeruginosa, respectively) and antioxidant (73% DPPH and 70% ABTS) properties. Therefore, the prepared hydrogels could be used as an effective controlled drug delivery system.

Investigation of the potential curative effects of Gui-Zhi-Jia-Ge-Gen decoction on wind-cold type of common cold using multidimensional analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gui-Zhi-Jia-Ge-Gen decoction (GJGD) is a classical Chinese medicine prescription that has been widely used in clinical practice for centuries. In recent times, TCM has received considerable attention for its potential efficacy in treating a wind-cold type of common cold. However, the effect of the Gui-Zhi-Jia-Ge-Gen decoction on the wind-cold type of common cold is still not fully understood, which presents challenges for both quality control, research and development. Furthermore, the identification of potential pharmacodynamic ingredients (PPIs) is important for developing quality control procedures for industrial and large-scale production. AIM OF THE STUDY: The aim of this study was to investigate the potential curative effect of Gui-Zhi-Jia-Ge-Gen decoction on wind-type of common cold using multidimensional qualitative analysis that combined water-decoction spectrums, in vivo plasma spectrums, and molecular docking to identify key constituents of GJGD. MATERIALS AND METHODS: Water-based GJGDs were formulated according to the clinical usage documented in ancient medical texts. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS) was combined with computer-aided modeling screening to identify GJGD PPIs in rats following oral administration. Molecular docking experiments were carried out to predict the binding affinity of the PPIs to tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1ß (IL-1ß). Finally, the active ingredients of GJGD were further validated through pharmacodynamic experiments by assessing their efficacy in treating a wind-cold type of common cold in rats. RESULTS: A total of 61 compounds were identified in the GJGD, 8 of which were detected in rat blood samples, providing stronger evidence for PPIs. Molecular docking also confirmed that these 8 compounds had a better affinity for TNF-α, IL-6, and IL-1ß. In animal studies, various doses of the GJGD groups and the positive control groups caused significant elevations (P < 0.05) in the levels of white blood cell count and lymphocyte ratio and caused a significant decrease (P < 0.05) in the monocyte ratio and neutrophilic granulocyte ratio compared to the model group. Organ indexes of the GJGD treated groups were higher than the model group (P < 0.05). Significant neutrophil infiltration, hemorrhage, compensatory vacuole, and interstitium proliferation were observed in the lung tissue of the model group. However, the lung tissues of the various dose groups that received GJGD showed a near normal appearance, except for slight thickening, interstitium proliferation, and compensatory vacuole in some areas. The GJGD was found to be effective against a cold-wind type of common cold, which is in accordance with molecular docking studies suggesting that GJGD may be effective against a cold-wind type of common cold. Finally, based on multidimensional analysis, 8 potential compounds in GJGD were identified as PPIs (puerarin, 3'-hydroxy puerarin, 3'- methoxy puerarin, daidzin, cinnamic acid, paeoniflorin, liquiritin, and glycyrrhizic acid). CONCLUSION: The present study combined water decoction spectral analysis, molecular docking, and in vivo blood plasma spectrum analysis to develop a multidimensional qualitative approach for the development of GJGD and to assess its effectiveness in a wind type of common cold in Sprague Dawley rats. Meanwhile, 8 compounds in the GJGD were identified as PPIs in this study, which may be useful in developing quality standards for complex TCM prescriptions.