Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2^-/- mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.
Alveolar Bone Loss/prevention & control* ; Animals ; Antioxidants/pharmacology* ; Inflammation ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; NF-E2-Related Factor 2/metabolism* ; Periodontitis/prevention & control* ; Succinates

OBJECTIVES: Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-‍α‍-tocopheryl succinic acid (VES), β‍-carotene (β‍-Ca), and L-lysine (Lys). METHODS: The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo. RESULTS: MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function. CONCLUSIONS This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
Mice ; Animals ; beta Carotene ; Lysine/pharmacology* ; Antioxidants/pharmacology* ; Quality of Life ; Paclitaxel/pharmacology* ; Apoptosis ; alpha-Tocopherol ; Succinates/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Neoplasms

A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson's disease (PD). However, the mechanisms underlying these links remain to be defined. Here, we investigated the impact of deregulation of intestinal dopamine D2 receptor (DRD2) signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration. Dopamine/dopamine signaling in the mouse colon decreased with ageing. Selective ablation of Drd2, but not Drd4, in the intestinal epithelium, caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge, and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota. Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential. This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival. These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects* ; Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Parkinson Disease ; Pyrrolidines ; Receptors, Dopamine D2/metabolism* ; Substantia Nigra ; Succinates

Cytomegalovirus (CMV) rarely manifests as cutaneous lesions in immunocompromised patients. Only 25 cases have been reported since 1991. It causes latent infection among exposed individuals but reactivation may occur in immunocompromised patients causing encephalitis, pneumonitis, colitis, retinitis and congenital fetal infection. Cutaneous manifestations of CMV infection usually present with various skin lesions such as ulcers, erosions, erythematous morbilliform rash, vesicles and bullae. We report a case of cutaneous CMV infection in an HIV-AIDS patient presenting as a persistent ulcerated plaque on the nose. The lesion slowly evolved into a plaque which partially destroyed the right alar rim. Skin punch biopsy showed perivascular giant cells with large eosinophilic inclusions resembling an owl's eye consistent with CMV infection. He was subsequently diagnosed with CMV retinitis because of blurring of vision and findings of retinal necrosis on fundoscopy. Oral valganciclovir 1800mg/day was given for 21 days. Significant thinning and drying of the plaque with no further progression of ulceration of the alar rim were noted.

Human ; Male ; Adult ; Acquired Immunodeficiency Syndrome ; Blister ; Colitis ; Cytomegalovirus ; Cytomegalovirus Retinitis ; Encephalitis ; Exanthema ; Ganciclovir ; Immunocompromised Host ; Pneumonia ; Strigiformes ; Succinates ; Ulcer

BACKGROUNDSarpogrelate is a selective 5-hydroxytryptamine (5-HT) receptor subtype 2A antagonist which blocks 5-HT induced platelet aggregation and proliferation of vascular smooth muscle cells. We compared the efficacy of sarpogrelate-based dual antiplatelet therapies for the prevention of restenosis and target lesion revascularization (TLR) rates comparing with that of clopidogrel after percutaneous endovascular interventions (EVIs) of femoropopliteal (FP) arterial lesions.

METHODSThis prospective, multicenter, randomized clinical trial recruited a total of 120 patients with successful EVI of FP lesions at seven centers across China between January 2011 and June 2012. Patients were randomized to receive either sarpogrelate (100 mg trice daily for 6 months, n = 63) or clopidogrel (75 mg once daily for 6 months, n = 57). All patients also received oral aspirin (100 mg once daily for 12 months). Clinical follow-up was conducted up to 12 months postprocedure.

RESULTSThere was no significant difference between the two groups in basic demographic data. The restenosis rate was higher in the clopidogrel group (22.80%) than in sarpogrelate group (17.50%), but there was no significant difference between these two groups (P = 0.465). The TLR rate, ipsilateral amputation rate, mortality in all-cause and bleeding rate were also similar in the two groups (P > 0.05).

CONCLUSIONSAspirin plus sarpogrelate is a comparable antithrombotic regimen to aspirin plus clopidogrel after EVI of FP arterial lesions. Dual antiplatelet therapies might play an important role in preventing restenosis after successful EVI of FP lesions.

Aged ; Arterial Occlusive Diseases ; drug therapy ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Peripheral Vascular Diseases ; drug therapy ; Popliteal Artery ; drug effects ; pathology ; Serotonin Antagonists ; therapeutic use ; Succinates ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo establish an HPLC method for the content determination of baicalin, wogonin, chlorogenic acid, caffeic acid, cichoric acid, corynoline and adenosine in Pudilan Xiaoyan oral liquid.

METHODThe analysis was performed on a Phenomenex Luna C18 column (4.6 mm x 250 mm, 5 µm) with a gradient mobile phase of methanol-0.1% trifluoroacetic acid solution system at flow rate of 1.0 mL · min(-1). The detective wavelength was at 280 nm. The column temperature was 30 °C.

RESULTThe standard curves of seven studied components show good linearity in their concentration ranges with r ≥ 0.999 6. The average recovery was 98.73%-102.1% with RSD less than 2.6%.

CONCLUSIONThe method is rapid, simple and accurate, and can be applied for the quality control of Pudilan Xiaoyan oral liquid.

Caffeic Acids ; analysis ; Chlorogenic Acid ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Flavanones ; analysis ; Flavonoids ; analysis ; Succinates ; analysis

In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
Antioxidants ; chemical synthesis ; metabolism ; pharmacology ; Cells, Cultured ; Curcuma ; chemistry ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hydrogen Peroxide ; metabolism ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Phthalic Acids ; chemical synthesis ; pharmacology ; Sesquiterpenes ; chemical synthesis ; pharmacology ; Succinates ; chemical synthesis ; pharmacology ; Superoxide Dismutase ; metabolism

BACKGROUND: Even though degrees of deformation of microform cleft lip are not high, it has to be corrected with various procedures upon conditions and areas since it has various expressions. Many studies have focused on the classifications and procedures, but there are only a few studies on how much these procedures are performed in the actual field. This study aims to analyze the utilization of various procedures upon major correction points. METHODS: A total of 52 patients who had been corrected by one surgeon from 1995 to 2011 were enrolled as subjects. Based on the medical records, it was checked whether the incision was made or not along with the correction procedures for alar base and philtral column, Cupid's bow, and vermillion free margin. RESULTS: In case of an incision, full incision (42 times) was conducted most frequently. For alar base and philtral column, muscle re-approximation (25 times) was performed most frequently. However, recently, it was shown that excision on only the affected area and correction with dermis were more likely to be used. For Cupid's bow and vermilion free margin, elliptical excision on the only affected area followed by re-approximation was performed most frequently for 46 times (Cupid's bow) and 44 times (vermilion free margin), respectively. CONCLUSION: For the correction of microform cleft lip, less invasive procedures are preferred. However, in the actual field, if needed, aggressive procedures consisting of incisions have been conducted to correction. These trends are somewhat changed to utilization of a simple procedure, such as excision on the modified area, followed by a re-approximation rather than complicated procedures using the muscle.
Cleft Lip ; Dermis ; Humans ; Medical Records ; Microfilming ; Muscles ; Succinates ; Surgical Procedures, Operative

This study reviews a case of sacral fracture with delayed onset neurological deficit that showed good results after decompressive surgery. The delayed neurological deficit appeared at 4 weeks after injury and it was treated with anterior decompression through transperitoneal approach. A 23-year-old woman was injured in a car accident and had bilateral pubic rami fractures and fractures of the sacral ala on the right side. She was treated with external fixation devices for approximately four weeks, but complained of pain and numbness. The dorsiflexion and plantalflexion of the right ankle was weakened and graded as grade 2. Preoperative pelvic and sacral radiographs, computed tomography, magnetic resonance imaging and electromyelography, and nerve conduction study were performed to identify the region of neurological deficit, and we decided to implement neurological decompression. By transperitoneal approach, we performed bone curratage and decompression around the region of sacral alar slope and S1 foramen. The pain and numbness of the right foot cleared up. Dorsiflexion and plantalflexion of the right ankle improved to grade 5. Anterior decompression by transperitoneal approach proved to bring satisfactory results in a patient, who presented delayed neurological deficit after sacral fracture.
Animals ; Ankle ; Decompression ; External Fixators ; Female ; Foot ; Humans ; Hypesthesia ; Magnetic Resonance Imaging ; Neural Conduction ; Succinates