Thai traditional medicines reduce CD147 levels in lung cells: Potential therapeutic candidates for cancers, inflammations, and COVID-19.

ETHNOPHARMACOLOGICAL RELEVANCE: The cluster of differentiation 147 (CD147) is identified as the signaling protein relevant importantly in various cancers, inflammations, and coronavirus disease 2019 (COVID-19) via interacting with extracellular cyclophilin A (CypA). The reduction of CD147 levels inhibits the progression of CD147-associated diseases. Thai traditional medicines (TTMs): Keaw-hom (KH), Um-ma-ruek-ka-wa-tee (UM), Chan-ta-lee-la (CT), and Ha-rak (HR) have been used as anti-pyretic and anti-respiratory syndromes caused from various conditions including cancers, inflammations, and infections. Thus, these medicines would play a crucial role in the reduction of CD147 levels. AIM OF THE STUDY: This article aimed to investigate the effects of KH, UM, CT, and HR for reducing the CD147 levels through in vitro study. Additionally, in silico study was employed to screen the active compounds reflexing the reduction of CD147 levels. MATERIALS AND METHODS: The immunofluorescent technique was used to evaluate the reduction of CD147 levels in human lung epithelial cells (BEAS-2B) stimulated with CypA for eight extracts of KH, UM, CT, and HR obtained from water decoction (D) and 70% ethanol maceration (M) including, KHD, UMD, CTD, HRD, KHM, UMM, CTM, and HRM. RESULTS: UM extracts showed the most efficiency for reduction of CD147 levels in the cytoplasm and perinuclear of BEAS-2B cells stimulated with CypA. Phenolic compounds composing polyphenols, polyphenol sugars, and flavonoids were identified as the major chemical components of UMD and UMM. Further, molecular docking calculations identified polyphenol sugars as CypA inhibitors. CONCLUSIONS: UMD and UMM are potential for reduction of CD147 levels which provide a useful information for further development of UM as potential therapeutic candidates for CD147-associated diseases such as cancers, inflammations, and COVID-19.

Gentiopicroside attenuates collagen-induced arthritis in mice via modulating the CD147/p38/NF-κB pathway.

Gentiopicroside (GEN) is a secoiridoid glycosides isolated from a traditional Chinese medicine Gentiana macrophylla Pall.. It exhibits potential activities in the treatment of inflammatory diseases. Here, we investigated whether GEN had the anti-rheumatoid arthritic activities in a model of rheumatoid arthritis, and explored its molecular mechanism. In vivo, the male C57BL/6J mice were injected chicken type II collagen to induce the animal model (collagen-induced arthritis, CIA). In vitro, we performed the research in rheumatoid fibroblast-like synoviocytes (FLS). In our study, it was innovatively authenticated that GEN treatment could not only reduce synovitis and inhibit the proliferation of RA FLS, but also relieve cartilage damage in CIA modal. More importantly, we firstly demonstrated that GEN treatment lessened the pain behaviors of CIA mice. In vivo and in vitro experiments confirmed that CD147 was the main target of GEN in attenuating RA symptoms for the first time. Next, we identified the downstream signaling pathway of CD147, and proved that the anti-RA effects of GEN were mediated by down-regulating the expression of p38, IκBα and p65 in vivo and in vitro assays. In conclusion, the data of this manuscript suggested that GEN treatment attenuated synovitis and cartilage destruction in CIA mice; the inhibitory effects on MMP secretion and the anti-rheumatic effects of GEN might be regulated by the CD147/p38/ NF-κB pathway. Accordingly, we found that GEN has the potential therapeutic effects for RA.

Pseudolaric Acid B Inhibits Proliferation, Invasion, and Angiogenesis in Esophageal Squamous Cell Carcinoma Through Regulating CD147.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system. Studies have shown that pseudolaric acid B (PAB) has several pharmacological effects like anti-microtubule, anti-angiogenesis, and antitumor functions, while the effect and mechanism of PAB on esophageal cancer are still unclear. This study was designed to investigate the effects of PAB on ESCC. METHODS: To study the effects of PAB on the biological function through a series of in vitro and in vivo experiments. RESULTS: The results revealed that PAB inhibited the proliferation, invasion, and migration, but promoted the apoptosis of ESCC. Moreover, PAB restrained the growth of cancer cells in vivo and inhibited the angiogenesis of HUVEC in mice with ESCC. CD147 expression was increased in the esophageal squamous cell lines, and interference with CD147 hindered the proliferation, invasion, and migration of ESCC cells, and inhibited the growth and angiogenesis of the esophageal squamous cell line. PAB reduced the expression of CD147 in vivo and in vitro. The expression of MMP2, 3, and 9 was increased after overexpression of CD147, which provided the opportunity to reverse the role of PAB in inhibiting proliferation, invasion, migration, and angiogenesis of ESCC. DISCUSSION: The results revealed that PAB inhibited the proliferation, invasion, migration, and angiogenesis of ESCC in vitro and in vivo by CD147. PAB is a promising monomer for therapy of ESCC, providing references for future research on ESCC treatment.

Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147).

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.

EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: Novel propositions.

Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with 'S' receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs.

Potential therapeutic targets and promising drugs for combating SARS-CoV-2.

As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147.

Shikonin, a traditional Chinese medicine, has been identified as being capable of inducing apoptosis in various tumors, including glioma, and is thus considered to be a promising therapeutic agent for tumor therapy. However, little is known about the molecular mechanism of shikonin in glioma. The present study investigated the influence of shikonin on the proliferation and apoptosis of glioma cells U251 and U87MG and explored the potential molecular mechanisms. It was identified that shikonin was able to induce apoptosis in human glioma cells in a time­ and dose­dependent manner, and a decreased expression level of cluster of differentiation (CD)147 was observed in shikonin­treated U251 and U87MG cells. Knockdown of CD147 inhibited U251 and U87MG cell growth, whereas CD147 overexpression enhanced cell growth and decreased shikonin­induced apoptosis. Additionally, an increased expression level of CD147 suppressed the elevated production of reactive oxygen species and mitochondrial membrane potential levels induced by shikonin. The data indicated that shikonin­induced apoptosis in glioma cells was associated with the downregulation of CD147 and the upregulation of oxidative stress. CD147 may be an optional target of shikonin­induced cell apoptosis in glioma cells.

Expression of Matrix Metalloproteinase-2, Tissue Inhibitor of Matrix Metalloproteinase-2 and CD147 in the Traditional Chinese Medicine "Compound T11" for Treatment of Chronic Liver Injury.

OBJECTIVES: To measure the expression of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-2, and CD147 in mice with chronic liver injury induced by carbon tetrachloride after treatment with the traditional Chinese medicine (TCM) "Compound T11". METHOD: Sixty male ICR mice were divided randomly into 6 groups of 10: control (C), model (M), low-dose treatment (LT; 50 mg/mL of Compound T11), medium-dose treatment (MT, 100 mg/mL), high-dose treatment (HT, 150 mg/mL), and positive drug treatment (YT, 67.5 mg/mL). Each group was modeled for 7 weeks. Groups M, LT, MT, HT, and YT were injected (s.c.) with 20% carbon tetrachloride diluted with olive oil, and group C was given olive oil in the same way twice a week. After modeling, the treatment groups were administered Compound T11 at the concentrations shown above by oral gavage daily for 2 weeks, while group C was given 0.5% carboxymethyl cellulose sodium. After the final treatment, mice were killed and their liver tissues were excised. Immunohistochemical staining was performed to measure the protein expression of MMP-2, TIMP-2, and CD147, and western blotting was used to measure the protein expression of MMP-2, TIMP-2, CD147, and α-smooth muscle actin (SMA). MMP-2, TIMP-2, and CD147 mRNA expression was determined by quantitative fluorescence real-time PCR. RESULTS: Compound T11 increased the protein expression of MMP-2 and CD147 and decreased the protein expression of TIMP-2 and α-SMA. CONCLUSIONS: Treatment of chronic liver injury by TCM Compound T11 may be associated with changes to the expression of MMP-2 and CD147, and the inhibition of TIMP-2 expression.

Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway.

Objective We investigated the protective effect of icariin on myocardial infarction-induced cardiac remodeling. Methods A cardiac remodeling model was constructed by ligating rats' coronary artery. Different icariin and CD147 concentrations were administered in the model group, and echocardiography was used to detect systolic function, screening out ideal experimental concentrations. The ventricular systolic function, myocardial apoptosis rate, and expression of collagen type I (Col I), Col III, CD147, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by hematoxylin-eosin staining, TUNEL assay, and western blot. MMP-9 activity was evaluated by gelatin zymography. Results The expression of Col I, Col III, CD147, and MMP-9 was higher, the expression of TIMP-1 was lower, and the maximal rates of left ventricular pressure rise and fall (+dp/dtmax and -dp/dtmax, respectively) were lower in model than control rats. The expression of CD147, MMP-9, Col I, and Col III was lower, the expression of TIMP-1 was higher, and the +dp/dtmax and -dp/dtmax were higher in the icariin than model group. The apoptosis rate was lower in the icariin and icariin + CD147 groups than control group. Conclusion Icariin attenuated myocardial apoptosis following myocardial infarction by apoptosis rate reduction and CD147/MMP-9 pathway inhibition.

Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines.

Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

[Significance of serum MMP-3, TIMP-1, and monocyte CD147 in rheumatoid arthritis patients of damp-heat Bi-syndrome and of cold-damp Bi-syndrome].

OBJECTIVE: To explore the clinical significance of serum matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and monocyte CD147 in rheumatoid arthritis (RA) patients of damp-heat Bi-syndrome (DHBS) and of cold-damp Bi-syndrome (CDBS). METHODS: The clinical data of 22 patients from inpatients and outpatients with RA were collected, and their peripheral blood was withdrawal. The disease activity scores [DAS28(4)] were assessed. The serum levels of MMP-3 and TIMP-1 were detected by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The mean fluorescence intensity (MFI) and the expression percentage of CD147 on CD14+ monocytes were detected by flow cytometry. The difference of each index between RA patients of DHBS and RA patients of CDBS was analyzed. RESULTS: The level of serum MMP-3 and the MFI of CD147 on the monocyte surface were obviously higher in RA patients of DHBS than in those of CDBS and the normal control group (P < 0.05). The concentration of serum TIMP-1 was obviously higher in RA patients of DHBS than in those of the normal control group (P < 0.05), while there was no statistical difference between the two syndrome types. The percentage of CD147 expression was obviously lower in DHBS than in those of CDBS and the normal control group (P < 0.05). CONCLUSIONS: Increased serum MMP-3 level of RA patients of DHBS might result in destroy of joint cartilages and sclerotin. The significant increase of MFI and decreased expression percentage of monocyte CD147 might be the results of increased disease activity of RA and monocyte migration to the synovial membrane tissue.

EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer.

BACKGROUND: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. RESULTS: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. CONCLUSION: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy.

Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer therapy.

The objective of this study was to evaluate extracellular matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other groups served as the control. In the residual tumor model, tumor growth of anti-EMMPRIN-treated group was successfully arrested for 21 days (15 ± 4 mm(3)), which was significantly lower than that of the EMMPRIN knockdown group (80 ± 15 mm(3); P=0.001) or the control group (240 ± 41 mm(3); P<0.001). In the established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by approximately 40% compared with the control, regardless of the dose amount. Ki67-expressed cell density of group 5 was 939 ± 150 mm(-2), which was significantly lower than that of group 4 (1709 ± 145 mm(-2); P=0.006). Microvessel density of group 5 (30 ± 6 mm(-2)) was also significantly lower than that of group 4 (53 ± 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 ± 22 µm(2)) was significantly larger than that of group 4 (113 ± 26 µm(2); P=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer and support its clinical translation.

Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.

1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. Human monocytic THP-1 cells were pretreated with 20-80 µg/mL artemisinin for 4 h or 1-10 µmol/L rottlerin for 1 h prior to stimulation with PMA (100 nmol/L) for another 48 h. Cells were collected to analyse the induction of EMMPRIN and MMP-9. Upstream pathway analysis using the PKCδ inhibitor rottlerin detected activation of the PKCδ/JNK/p38/ERK pathway. 3. Artemisinin (20-80 µg/mL) significantly inhibited the induction of EMMPRIN and MMP-9 at both the transcriptional and translational levels in a dose-dependent manner in PMA-induced macrophages. In addition, artemisinin (20-80 µg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 µmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.

CD147, a gamma-secretase associated protein is upregulated in Alzheimer's disease brain and its cellular trafficking is affected by presenilin-2.

Gamma-secretase activity has been extensively investigated due to its role in Alzheimer's disease. Here, we studied the association of CD147, a transmembrane glycoprotein belonging to the immunoglobulin family, with gamma-secretase and its expression in Alzheimer's disease and control tissues. Subcellular fractionation of postmitochondrial supernatant from rat brain on step iodixanol gradient in combination with co-immunoprecipitation using an anti-nicastrin antibody showed association of limited amount of CD147 to gamma-secretase. By immunoblotting of postnuclear pellets from Alzheimer's disease and control human brain tissues we showed that CD147 with molecular weight 75 kDa is upregulated in frontal cortex and thalamus of the Alzheimer's disease brains. Immunohistochemistry of brain tissues from Alzheimer's disease and control revealed specific upregulation of CD147 in neurons, axons and capillaries of Alzheimer's disease frontal cortex and thalamus. The effect of presenilin-1 and -2, which are the catalytic subunits of gamma-secretase, on CD147 expression and subcellular localization was analyzed by confocal microscopy in combination with flow cytometry and showed that PS2 affected the subcellular localization of CD147 in mouse embryonic fibroblast cells. We suggest that a small fraction of CD147 present in the brain is associated with the gamma-secretase, and can be involved in mechanisms dysregulated in Alzheimer's disease brain.

[High glucose and tea polyphenols on expression of matrix metalloproteinase-2 and extracellular matrix metalloproteinase inducer in human umbilical vein endothelial cells].

OBJECTIVE: To investigate the effects of high glucose on expression of matrix metalloproteinase-2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were cultured in DMEM media containing high glucose with or without polyphenols for 24 hours respectively. The activity of MMP-2 in the supernatant was detected by zymography. The expression of MMP-2 mRNA and protein in HUVECs were detected by RT-PCR and Western blot respectively. The expression of EMMPRIN mRNA and protein in the cells were determined by RT-PCR as well as immunocytochemistry and Western blot respectively. RESULTS: The expression of MMP-2 and EMMPRIN mRNA were suppressed by a high concentration of glucose. Both the MMP-2 activity and protein level of EMMPRIN expression were also significantly decreased. Polyphenols abolished all the above changes of HUVECs induced by a high glucose level (P < 0.05). CONCLUSIONS: An acute high glucose stimulation down-regulates the activity of MMP-2, the expressions of MMP-2 and EMMPRIN at RNA and protein levels in the endothelial cells, which may play an important roles in diabetic vascular complications in the early phase. Polyphenols treatment can diminish the detrimental effects of high glucose on HUVECs.

Dietary pectin up-regulates monocaboxylate transporter 1 in the rat gastrointestinal tract.

This work was undertaken to study the effect of pectin feeding on the expression level, cellular localization and functional activity of monocarboxylate transporter 1 (MCT1) in the gastrointestinal tract of rats. The results indicated that MCT1 protein level was significantly increased along the entire length of the gastrointestinal tract of pectin-fed rats in comparison with control animals. Immunohistochemical analysis revealed an increase in MCT1 in the stratified squamous epithelia of the forestomach as well as in the basolateral membranes of the cells lining the gastric pit of the glandular stomach of pectin-fed rats when compared with control animals. The parietal cells, which showed barely any or no detectable MCT1 in the control group, exhibited a strong intensity of MCT1 on the basolateral membranes in pectin-fed rats. In the small intestine of pectin-fed rats, strong immunopositivity for MCT1 was detected in the brush border and basolateral membranes of the absorptive enterocytes lining the entire villi, while in control rats, weak reactivity was detected on the brush border membrane in a few absorptive enterocytes in the villus tip. In the large intestine of control animals, MCT1 was detected on the basolateral membranes of the epithelia lining the caecum and colon. This staining intensity was markedly increased in pectin-fed rats, along with the appearance of strong reactivity for MCT1 on the apical membranes of the surface and crypt epithelia of caecum and colon. Our results also showed that MCT1 co-localizes with its chaperone, basigin (CD147), in the rat gastrointestinal tract, and that the pectin feeding increased the expression of CD147. In vivo functional studies revealed an enhanced acetate absorption in the colon of pectin-fed in comparison with control animals. We conclude that MCT1 is up-regulated along the gastrointestinal tract of pectin-fed rats, which might represent an adaptive response to the increased availability of its substrates.

Ginkgo biloba extract prevents glucose-induced accumulation of ECM in rat mesangial cells.

Pathological remodeling characterized by extracellular matrix (ECM) accumulation contributes to diabetic nephropathy (DN). This study evaluated the effects of Ginkgo biloba extract (GbE) on the metabolism of the ECM in rat mesangial cells cultured in hyperglycemic conditions. The cultured mesangial cells in high glucose conditions were allotted into six groups: normal control group, high glucose group, low concentration of GbE group, moderate concentration of GbE group, high concentration of GbE group, and captopril group. In the presence of high glucose, the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN) were decreased significantly, and the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) were increased significantly. These changes were reversed by GbE. GbE lowered the levels of transforming growth factor-beta(1) (TGF-beta(1)), insulin-like growth factor-1 (IGF-1) and connective tissue growth factor (CTGF) of the high glucose group. Furthermore, GbE also decreased the expressions of collagen IV and laminin of the high glucose group. In summary, the results suggest that GbE postpones the extracellular matrix accumulation by inhibiting the synthesis of ECM and promoting the degradation of ECM, and therefore, is a potential drug for the prevention and treatment of DN.

Identification of gene transcripts in rat frontal cortex that are regulated by repeated electroconvulsive seizure treatment.

BACKGROUND/AIMS: Electroconvulsive therapy (ECT) is an effective treatment modality for severe psychiatric disorders. Many studies have suggested that the therapeutic efficacy of ECT can be attributed to the structural and functional readjustment of the brain cells, which is mediated by differential gene expression in the brain. The aim of this study is to understand the molecular mechanism of ECT. METHODS: We used microarray-based gene expression profiling technology and real-time quantitative PCR (RT-qPCR) to screen differentially expressed genes in the brain in a rat model of ECT. RESULTS: Four upregulated and three downregulated genes were identified in this study. The 4 upregulated genes are S100 protein, beta polypeptide (S100b), S100 calcium binding protein A13_predicted (S100a13_predicted), diazepam-binding inhibitor (Dbi), and YKT6 homolog (S. Cerevisiae) (Ykt6), respectively; while the 3 downregulated genes are basigin (Bsg), histidine triad nucleotide binding protein 1(Hint 1), and neural precursor cell expressed, developmentally downregulated gene 8 (Nedd8), respectively. CONCLUSION: In view of the neurobiological function of these genes and their relevance to mental disorders, repeated ECS can affect gene expression involved in the neurotransmission and synaptic plasticity, which may account for the clinical effects of ECT.