Reduction Of Inflammatory Response Research Articles

Glucans: A Therapeutic Alternative for Sepsis Treatment

Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was β-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.

The impact of nursing interventions on the rehabilitation outcome of patients after lumbar spine surgery

BackgroundThis study aimed to investigate the impact of nursing interventions on the rehabilitation outcomes of patients after lumbar spine surgery and to provide effective references for future postoperative care for patients undergoing lumbar spine surgery.MethodsThe study included two groups: a control group receiving routine care and an observation group receiving additional comprehensive nursing care. The comprehensive care encompassed postoperative rehabilitation, pain, psychological, dietary management, and discharge planning. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), Short-Form 36 (SF-36) Health Survey, self-rating depression scale (SDS) and self-rating anxiety scale(SAS) were used to assess physiological and psychological recovery. Blood albumin, haemoglobin, neutrophil counts, white blood cell counts, red blood cell counts, inflammatory markers (IL-6, IL-10, and IFN-γ) were measured, and the incidence of postoperative adverse reactions was also recorded.ResultsPatients in the observation group exhibited significantly improved VAS, ODI, SF-36, SDS and SAS scores assessments post-intervention compared to the control group (P < 0.05). Moreover, levels of IL-6, IL-10, and IFN-γ were more favorable in the observation group post-intervention (P < 0.05), indicating a reduction in inflammatory response. There was no significant difference in the incidence of postoperative adverse reactions between the groups (P > 0.05), suggesting that the comprehensive nursing interventions did not increase the risk of adverse effects.ConclusionComprehensive nursing interventions have a significant impact on the postoperative recovery outcomes of patients with LSS, alleviating pain, reducing inflammation levels, and improving the overall quality of patient recovery without increasing the patient burden. Therefore, in clinical practice, it is important to focus on comprehensive nursing interventions for patients with LSS to improve their recovery outcomes and quality of life.

Effects of sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute on Metabolic Regulation in Sprague-Dawley Rats.

In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague-Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing the total sn-2 palmitic TAGs and OPL to OPO ratio in HMFS could significantly influence glycine, serine and threonine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism, bile acid biosynthesis, and taurine and hypotaurine metabolism pathways in rats after 4 weeks of feeding, which were mainly related to lipid, bile acid and energy metabolism. Meanwhile, the up-regulation of taurine, L-tryptophan, and L-cysteine, and down-regulations of lysoPC (18:0) and hypoxanthine would contribute to the reduction in inflammatory response and oxidative stress, and improvement of immunity function in rats. In addition, analysis of targeted biochemical factors also revealed that HMFS-fed rats had significantly increased levels of anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), and decreased levels of pro-inflammatory factors (IL-6 and TNF-α) and malondialdehyde (MDA), compared with those of the control fat-fed rats. Collectively, these observations present new in vivo nutritional evidence for the metabolic regulatory effects of the TAG structure and composition of human milk fat substitutes on the host.

Osseointegrative and immunomodulative 3D-Printing Ti6Al4V-based implants embedded with biogenic hydroxyapatite

Although titanium-based metal implants have become a game changer in dental and orthopedic therapies, they still have several problems such as late osseointegration and immune response. In this study, we present a novel strategy to develop Ti6Al4V-based implants embedded with biogenic hydroxyapatite derived from equine bone to overcome these problems. A selective laser melting technique was employed for facile fabrication with flexible fusing feedstock and regular uniform distribution of equine bone. The physicochemical characteristics, cell attachment and proliferation, osteogenic differentiation, osseointegration, inflammatory response, and metabolomics of the developed Ti6Al4V/equine bone composite were then investigated. The Ti6Al4V-based composite integrated with equine bone at a certain concentration has improved the crystalline structure (β-Ti) suitable for implantation and exhibited higher hydrophilicity and protein adsorption. They significantly promoted cell attachment, osteogenic differentiation, and anti-inflammatory effects in vitro. In vivo study confirmed the osseointegration and alleviated inflammatory responses. Furthermore, the Ti6Al4V-based implants integrated with equine bone significantly reduced metabolites associated with inflammatory responses both in vitro and in vivo. The observed reduction in inflammatory responses suggests a subsequent promotion of osteogenesis. These promising results position the Ti6Al4V-based implant integrated with equine bone as a potential candidate for replacing conventional dental and orthopedic implants.

Mechanisms of action of Shizhenqing granules for eczema treatment: Network pharmacology analysis and experimental validation

BackgroundJiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation. MethodsThe main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the “herbal compound–potential target” and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema. ResultsUsing UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats. ConclusionThis study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

Gui ShenWan prevent premature ovarian insufficiency by modulating autophagy and angiogenesis via facilitating VDR

Ethnopharmacological relevanceGui Shen Wan (GSW) stands out as a promising therapeutic approach for addressing Premature Ovarian Insufficiency (POI). With deep roots in traditional medicine, GSW highlights the ethnopharmacological significance of herbal interventions in addressing nuanced aspects of women's health, with a specific emphasis on ovarian functionality. Recognizing the importance of GSW in gynecological contexts resonates with a rich tradition of using botanical formulations to navigate the intricacies of reproductive health. Delving into GSW's potential for treating POI emphasizes the crucial role of ethnopharmacological insights in guiding modern research endeavors. Aim of the studyGSW is extensively utilized in gynecological disorders and has recently emerged as a potential therapeutic approach for POI. The present investigation aimed to assess the efficacy of GSW in treating POI in rats and elucidate its underlying molecular mechanisms. Materials and methodsThe study employed GSW for POI treatment in rats. GSW, prepared as pills, underwent HPLC fingerprinting for quality control. Reagents and drugs, including VCD and dehydroepiandrosterone (DHEA), were sourced from reputable providers. Eighty Sprague-Dawley rats were categorized into groups for POI induction and treatment. Ovarian tissue underwent HE staining, immunohistochemical staining, Western Blot, qRT-PCR, and vaginal secretion testing. ELISA was utilized for target molecule detection. This methodology ensures a robust and reliable experimental framework. ResultsThe results highlight a robust collaborative improvement in POI among rats subjected to combined GSW and DHEA treatment. Particularly noteworthy is the substantial enhancement in the expression of vascular regeneration-related molecules—VDR-Klotho-VEGFR—accompanied by a significant elevation in autophagy levels. Post-GSW administration, rat ovarian morphology demonstrated increased stability, hormone levels exhibited more consistent maintenance, and there was a marked reduction in inflammatory response compared to other groups (p < 0.01). Furthermore, GSW intervention resulted in a more pronounced upregulation of ovarian autophagy (p < 0.05). ConclusionBy modulating VDR-Klotho signaling, GSW exerts regulatory control over ovarian autophagy and vascular regeneration, thereby mitigating the occurrence and progression of POI in rats.

Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway

Ethnopharmacological relevanceDiabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. Aim of the study and Materials and methodsIn this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. ResultsThe findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1β, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. ConclusionsPTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

The effects of Annual SZ drug on dynamic changes in lymphocytes and cytokines of COVID-19 patients: A randomized clinical trial

BackgroundThe search for a potent anti-coronavirus therapy has remained an overwhelming task since the outbreak of COVID-19. Annual SZ is a novel formulation of artemisinin and its derivatives. We aim to investigate the effect of Annual SZ on clinical outcomes, cellular immune responses, and cytokine changes in COVID-19 patients. MethodsThis study included 80 COVID-19 hospitalized patients, which were randomly allocated into two groups (intervention and control). Both groups received standard supportive treatment. In addition, the intervention group (n = 40) received Annual SZ syrup, and the control group (n = 40) received a placebo. Dynamic changes in lymphocytes, cytokines, and clinical status were evaluated since hospital admission to 7 and 14 days after treatment. ResultsThe dynamic count of total T lymphocytes and T lymphocyte subsets (CD4+ and CD8+) in the Annual SZ group was significantly higher than the placebo group (p < 0.05). In addition, Programmed Death 1 (PD-1) was significantly increased in the CD4+ and CD8+ T cells in the placebo group compared with the Annual SZ group (p < 0.05). Also, the CD4+/CD8+ ratio was not significantly different between the groups (p > 0.9). Moreover, IL-6 levels were significantly reduced (p < 0.05), while IL-4 and IFN-γ levels were not statistically different between the two groups (p > 0.05). ConclusionThis research indicated that the Annual SZ syrup significantly improved clinical status and lymphocyte frequency with less exhaustion of T lymphocytes and a reduction of inflammatory responses, which seems to be beneficial in the treatment process of COVID-19 patients.

Reduction of inflammatory response after ischemia-reperfusion injury in rats with panax notoginseng saponins by regulating nucleotide-bound oligomerized domain-like receptor protein 1(NLRP1)/Caspase-1 signaling via Cezanne

Acute ischemic stroke (AIS) is featured as damage of blood-brain barrier in severe cases, which leads to brain tissue damage. Panax notoginseng saponins (PNS), because of its anti-inflammatory effect, can reduce the inflammatory response caused by ischemia-reperfusion, thereby reducing the degree of damage to the blood-brain barrier. Studies on AIS have confirmed that, Cazenne has an anti-inflammatory effect, but specific mechanism by which PNS regulates Cazenne to reduce the inflammatory response after cerebral ischemia-reperfusion injury (IRI) is still unclear. Therefore, this study explored PNS’ role in inhibiting the inflammatory response after cerebral IRI through Cezanne. Sprague-Dawley (SD) rats were randomly grouped and then assigned into sham operation group (sham), model group (MCAO), model+PNS (MCAO+PNS), model+PNS+Cezanne silencing lentivirus (MCAO+PNS+shCezanne), and model+PNS+empty carrier (MCAO+PNS+shNC). Neurological function was scored by mNSS while cerebral infarction volume was tested by TCC staining. The brain was tested by dry and wet method, while levels of inflammatory factors and NLRP1 and Caspase-1 were detected by ELISA, Western blot, and Cazenne expression was detected by immunofluorescence. PNS reduced the expression of pro-inflammatory factors in MCAO rats, by mainly downregulating NLRP-1 and Caspase-1. By upregulating Cezanne and inflammatory factors downstream NLRP1/Caspase-1 pathway was inhibited, thereby improving the inflammation in the rats after IRI. PNS inhibited the activity of NLRP1/Caspase-1 signaling pathway through Cezanne, thereby reducing inflammatory factors in the brain after cerebral IRI, and reducing inflammatory response.

Aerosol Delivery of Palivizumab in a Neonatal Lamb Model of Respiratory Syncytial Virus Infection.

(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the "proof-of-principle" effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings.

Polyurethane-based nanofibrous mat containing porphyrin with photosensitivity and bactericidal properties can promote cutaneous tissue healing in rats

The regeneration of cutaneous tissue is one of the most challenging issues in human regenerative medicine. To date, several studies have been done to promote cutaneous tissue healing with minimum side effects. The healing potential of polyurethane (PU)/Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone) (PCEC)/chitosan (CS) (PCS) nanofibrous mat with cationic photosensitizer meso tetrakis (N-methyl pyridinium-4-yl) porphyrin tetratosylate salt (TMP) was examined. The CS tripolyphosphate nanoparticles (CSNPs) were prepared and loaded by TMP to provide an efficient drug release system (TMPNPs) for delivery of TMP to promote wound healing. In in vitro setting, parameters such as bactericidal effects, cytocompatibility, and hemolytic effects were examined. The healing potential of prepared nanofibrous mats was investigated in a rat model of full-thickness cutaneous injury. PCS/TMP/TMPNPs nanofibers can efficiently release porphyrin in the aqueous phase. The addition of TMPNPs and CS to the PU backbone increased the hydrophilicity, degradation, and reduced mechanical properties. The culture of human fetal foreskin fibroblasts (HFFF2) on PCS/TMP/TMPNPs scaffold led to an increased survival rate and morphological adaptation analyzed by MTT and SEM images. Irradiation with a red laser (635 nm, 3 J/cm2) for the 30 s reduced viability of S. aureus and E. Coli bacteria plated on PCS/TMP and PCS/TMP/TMPNPs nanofibrous mats compared to PU/PCEC (PC) and PU/PCEC/CS (PCS) groups, indicating prominent antibacterial effects of PCS/TMP and PCS/TMP/TMPNPs nanofibrous (p < 0.05). Data indicated that PCS/TMP/TMPNPs mat enhanced healing of the full-thickness excisional wound in a rat model by the reduction of inflammatory response and fibrotic changes compared to the PC, and PCS groups (p < 0.05). Immunofluorescence imaging indicated that levels of Desmoglein were increased in rats that received PCS/TMP/TMPNPs compared to the other groups. It is found that a PU-based nanofibrous mat is an appropriate scaffold to accelerate the healing of injured skin.Graphical abstract

Imiquimod-Loaded Chitosan-Decorated Di-Block and Tri-Block Polymeric Nanoparticles Loaded In Situ Gel for the Management of Cervical Cancer.

Cervical intraepithelial neoplasia, the predisposing factor for cervical cancer (CC), is caused by human papillomavirus (HPV) infection and can be treated with imiquimod (IMQ). However, poor water solubility and side effects such as local inflammation can render IMQ ineffective. The aim of this study is to design a prolonged release nano system in combination with mucoadhesive-thermosensitive properties for an effective vaginal drug delivery. Polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly lactide-co-caprolactone (PLA-PCL), and poly L-lactide-co-caprolactone-co-glycolide (PLGA-PCL) were used to create IMQ nanoparticles. Chitosan (CS) was then added to the surfaces of the IMQ NPs for its mucoadhesive properties. The NPs were then incorporated into poloxamer hydrogels. The NPs' size and morphology, encapsulation efficiency (EE), in vitro drug release, gel characterization, ex vivo drug permeation, and in vitro safety and efficacy were characterized. Two batches of NPs were prepared, IMQ NPs and CS-coated NPs (CS-IMQ NPs). In general, both types of NPs were uniformly spherical in shape with average particle sizes of 237.3 ± 4.7 and 278.2 ± 5.4 nm and EE% of 61.48 ± 5.19% and 37.73 ± 2.88 for IMQ NPs and CS-IMQ NPs, respectively. Both systems showed prolonged drug release of about 80 and 70% for IMQ NPs and CS-IMQ NPs, respectively, within 48 h. The gelation temperatures for the IMQ NPs and CS-IMQ NPs were 30 and 32 °C, respectively; thus, suitable for vaginal application. Although ex vivo permeability showed that CS-IMQ NPs showed superior penetration compared to IMQ NPs, both systems enhanced drug penetration (283 and 462 µg/cm2 for IMQ NPs and CS-IMQ NPs, respectively) relative to the control (60 µg/cm2). Both systems reduced the viability of cervical cancer cells, with a minimal effect of the normal vaginal epithelium. However, IMQ NPs exhibited a more pronounced cytotoxic effect. Both systems were able to reduce the production of inflammatory cytokines by at least 25% in comparison to free IMQ. IMQ and CS-IMQ NP in situ gels enhanced stability and drug release, and improved IMQ penetration through the vaginal tissues. Additionally, the new systems were able to increase the cytotoxic effect of IMQ against CC cells with a reduction in inflammatory responses. Thus, we believe that these systems could be a good alternative to commercial IMQ systems for the management of CC.

CD147 monoclonal antibody attenuates abdominal aortic aneurysm formation in angiotensin II-Infused apoE-/- mice.

Abdominal aortic aneurysm (AAA) is a life threatening vascular disease. Our previous study reported the upregulation of CD147 expression in human aortic aneurysms. In this study, we injected apoE-/- mice intraperitoneally with CD147 monoclonal antibody or IgG control antibody to observe its effect on Angiotensin II (AngII) induced AAA formation. ApoE-/- mice were randomly divided into an AngⅡ+CD147 antibody group (n=20) and an AngⅡ+IgG antibody group (n=20). The Alzet osmotic minipump was implanted subcutaneously into the backs of mice to infuse AngII (1000ng/kg/min) for 28days and subsequently treated with CD147 monoclonal antibody or control IgG mAb (10μg/mouse/day) beginning one day after surgery. Body weight, food intake, drinking volume and blood pressure were measured weekly throughout the study. After 4weeks of injection, routine bloodwork measuring liver function, kidney function and lipid levels were recorded. Hematoxylin and eosin (H&E), Masson's trichrome, and Elastic van Gieson (EVG) staining were used to evaluate the pathological changes in blood vessels. In addition, Immunohistochemical assay was used to detect infiltration of inflammatory cells. Tandem mass tag (TMT)-based proteomic analysis was used to define differentially expressed proteins (DEPs) using a p-value<0.05 and fold change>1.2 or<0.83 as the threshold. Subsequently, we conducted protein-protein interaction (PPI) network and GO enrichment analysis to determine the core biological function altered after CD147 antibody injection. The CD147 monoclonal antibody suppresses Ang II-induced AAA formation in apoE-/- mice and reduced aortic expansion, elastic lamina degradation, and inflammatory cells accumulation. Bioinformatics analysis showed that Ptk6, Itch, Casp3, and Oas1a were the hub DEPs. These DEPs in the two group were mainly involved in collagen fibril organization, extracellular matrix organization, and muscle contraction. These data robustly demonstrated that CD147 monoclonal antibody suppresses Ang II-induced AAA formation through reduction of inflammatory response and regulation of the above defined hub proteins and biological processes. Thus, the CD147 monoclonal antibody might be a promising target in the treatment of abdominal aortic aneurysm.

Mitophagy deficiency activates stimulator of interferon genes activation and aggravates pathogenetic cardiac remodeling

Stimulator of interferon genes (STING) has recently been found to play a crucial role in cardiac sterile inflammation and dysfunction. The role of stimulator of interferon genes (STING) in cardiac sterile inflammation and dysfunction has been recently discovered. This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway. To investigate this, transverse aortic constriction (TAC) was performed on STING knockout mice to induce pressure overload-induced cardiac remodeling. Subsequently, cardiac function, remodeling, and inflammation levels were evaluated. The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin II (Ang II)-stimulated cardiac fibroblasts. Loss of STING expression led to a significant reduction in inflammatory responses, mitochondrial fragmentation, and oxidative stress in the heart, resulting in attenuated cardiac remodeling and dysfunction. Furthermore, the exacerbation of pressure overload-induced STING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was suppressed through the silencing of Parkin, an E3 ubiquitin ligase. Taken together, these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation. Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.

GOLPH3 promotes endotoxemia-induced liver and kidney injury through Golgi stress-mediated apoptosis and inflammatory response

Sepsis is a serious clinical condition characterized by a systemic inflammatory response, a leading cause of acute liver and kidney injury, and is associated with a high morbidity and mortality. Understanding the molecular mechanisms underlying the acute liver and kidney injury is crucial for developing an effective therapy. Golgi apparatus plays important roles and has various substrates mediating cellular stress responses. Golgi phosphoprotein 3 (GOLPH3), linking Golgi membranes to the cytoskeleton, has been identified as an important oncogenic regulator; however, its role in endotoxemia-induced acute liver and kidney injury remains elusive. Here, we found that upregulation of GOLPH3 was associated with endotoxemia-induced acute liver and kidney injury. Lipopolysaccharide (LPS) treatment increased Golgi stress and fragmentation, and associated pro-inflammatory mediator (Tnfα, IL-6, and IL-1β) production in vivo and in vitro. Interestingly, the downregulation of GOLPH3 significantly decreased LPS-induced Golgi stress and pro-inflammatory mediators (Tnfα, IL-6, Mcp1, and Nos2), and reversed apoptotic cell deaths in LPS-treated hepatocytes and renal tubular cells. GOLPH3 knockdown also reduced inflammatory response in LPS-treated macrophages. The AKT/NF-kB signaling pathway was suppressed in GOLPH3 knockdown, which may be associated with a reduction of inflammatory response and apoptosis and the recovery of Golgi morphology and function. Taken together, GOLPH3 plays a crucial role in the development and progression of acute liver and kidney injury by promoting Golgi stress and increasing inflammatory response and apoptosis, suggesting GOLPH3 as a potential therapeutic target for endotoxemia-induced tissue injury.

Resveratrol in Cancer Treatment with a Focus on Breast Cancer.

Acute liver injury (ALI) is a critical and fatal disorder associated with excessive Although considerable advances have been made in the early diagnosis and treatment of breast cancer, it is still one of the major causes of global cancer-related death in women over the last several decades. Phytochemicals have been shown to be promising agents in the prevention and treatment of breast cancer. Resveratrol is an important plant-derived polyphenolic compound with a variety of potent biological activities. It has been suggested that resveratrol can be used to prevent and treat various types of cancer, including breast cancer. Resveratrol can affect numerous signaling pathways in vitro, leading to the induction of cell cycle arrest and apoptosis, suppression of proliferation, reduction of inflammatory responses, and the inhibition of angiogenesis and metastasis. Nevertheless, studies of resveratrol in animal models of breast cancer have so far been disappointing.

Interplay between autophagy and coronavirus: autophagy mechanism

&amp;lt;p&amp;gt;&amp;amp;nbsp;&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;Regardless of the fascinating progress of humanity, biotechnology and medicine, the outbreak of the global pandemic of the SARS-CoV-2 virus has shown us that we are just as vulnerable as in previous eras when communicable diseases decimated the world&amp;amp;rsquo;s population. But the discoveries made so far at the molecular level allow us to connect knowledge interdisciplinary and find solutions and therapeutic strategies where there seems to be no link. It was the previous coronavirus infections that served as a homologous model for finding the connection between the SARS-CoV-2 virus and autophagy. Autophagy, a conserved universal process of all eukaryotic cells responsible for cell survival under stressful circumstances, has been shown to play a significant role in viral invasions. It contributes to both direct and indirect antiviral responses such the elimination of viruses, the presentation of their antigens, and the reduction of inflammatory responses. The autophagy machinery of host cells can, however, be suppressed, evaded, or used by viruses to their benefit. Therefore, autophagy has an ambiguous role in coronavirus-related infections, especially in COVID-19.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;amp;nbsp;&amp;lt;/p&amp;gt;

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats.

The present study evaluated the anti-arthritic impact of combined crocin and curcumin on Adjuvant Induced Arthritis (AIA) in rats. Arthritis model was induced in rats by injecting Complete Freund's adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti-arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats. The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlβ and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg respectively), as well as MTX revealed suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti-arthritic effects owing to their anti-inflammatory effects. Therefore, crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis .

Salivary levels of BAFF, TWEAK, and soluble CD163 and salivary arginase activity before and after periodontal treatment.

To monitor salivary B-cell activating factor (BAFF), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and soluble (s)CD163 levels and arginase activity in periodontitis patients following nonsurgical periodontal treatment. BAFF, TWEAK, and sCD163 and arginase are associated with activities of B cells and macrophages, which are important regulators of periodontal immune-inflammatory response and healing following treatment. Increased salivary BAFF and sCD163 levels and arginase activity in periodontitis have been demonstrated, but their changes following treatment have not been evaluated before. Forty-four Stage III/IV periodontitis patients and 35 periodontally healthy controls were included in the study. Full-mouth periodontal measurements were recorded and unstimulated saliva was obtained from all participants at baseline. Sample collection and measurements were repeated in periodontitis patients at 2, 6, 12, and 24 weeks following full-mouth scaling and root debridement, whereas controls were only seen at baseline. BAFF, TWEAK, and sCD163 levels were analyzed with bead-based multiplexed immunoassay. Arginase activity was measured with Chinard's method. BAFF (p < .001) and sCD163 (p = .003) levels and arginase activity (p < .015) were higher in periodontitis patients compared to healthy controls. BAFF levels (p < .001) and arginase activity (p < .001) of periodontitis patients were reduced at 2 weeks posttreatment and continued to decrease up to 6 (p = .038) and 12 weeks (p = .024), respectively. The reduction of sCD163 levels became significant (p = .003) at 24 weeks posttreatment. The decrease in salivary BAFF levels 2 weeks after periodontal treatment indicates a change in cell signaling toward limited B-cell activation. Decreasing arginase activity similarly reflects a significant reduction in inflammatory response. The reduction in sCD163 levels that are observed at 24 weeks may reflect a longstanding anti-inflammatory macrophage activation, given their multiple functions in immune response, inflammation, and healing.

Research progress on the effects of novel hypoglycemic drugs in diabetes combined with myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) reperfusion is associated with ischemia/reperfusion (I/R) injury, which leads to enlarged myocardial infarction size, poor healing of the infarcted myocardium, and poor left ventricular remodeling, thus increasing the risk of major adverse cardiovascular events (MACEs). Diabetes increases myocardial susceptibility to I/R injury, decreases myocardial responsiveness to cardioprotective strategies, exacerbates myocardial I/R injury, and expands the infarct size of AMI, thereby increasing the incidence of malignant arrhythmias and heart failure. Currently, evidence regarding pharmacological interventions for diabetes combined with AMI and I/R injury is lacking. Traditional hypoglycemic drugs have a limited role in the prevention and treatment of diabetes combined with I/R injury. Current evidence suggests that novel hypoglycemic drugs may exert a preventive effect on diabetes combined with myocardial I/R injury, especially glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-dependent glucose transporter protein 2 inhibitors (SGLT2i), which may increase coronary blood flow, reduce acute thrombosis, attenuate I/R injury, decrease myocardial infarction size, inhibit structural and functional remodeling of the ischemic heart, improve cardiac function, and reduce the occurrence of MACEs of diabetes patients combined with AMI via mechanisms such as reduction of inflammatory response, inhibition of oxidative stress, and improvement of vascular endothelial function. This paper will systematically elaborate the protective role and molecular mechanisms of GLP-1 RA and SGLT2i in diabetes combined with myocardial I/R injury, aiming to provide clinical assistance.