Bibliometric analysis of mucosal immunity in IgA nephropathy from 1990 to 2022.

OBJECTIVE: The study aimed to conduct a bibliometric analysis of mucosal immunity in IgA nephropathy (IgAN) and indicate its current status, hot sopts, and direction of future studies. METHODS: The literature data was collected from the Web of Science Core Collection. CiteSpace 6.1.R3 was employed to conduct a visualization bibliometric analysis of mucosal immunity in IgA nephropathy, including authors, countries, journals, keywords, organizations, references, the bursts of keywords and references, and the timeline of keyword clusters and reference clusters. RESULTS: A total of 315 publications from 1990 to 2022 were included. The number of articles in this field has increased in recent years. Suzuki H, Coppo R, and Feehally J took the first place parallelly with 18 articles. Japan contributes the most articles, accounting for 27.3% of all the publications. The institutions with the most publications were Juntendo University and University of Alabama Birmingham. 453 keywords were concluded in the analysis, which mainly focus on the mucosal pathogenesis and therapy of the IgAN. The top five co-cited reference cluster are "aberrantly glycosylated IgA," "corticosteroids," "animal models," "o-glycosylationm" and "microRNA-630." The most recently burst of keyword is "tonsillectomy" and "gut." CONCLUSION: This was the first bibliometric analysis to systematically analyze the mucosal immunity in IgAN, which obtained the current status and indicated the future research hotspots and development trends. The gut microbiota and the related therapy-targeted mucosal immunity might be the future research hotspot.

Prognostic effect of pulmonary hypertension in patients with chronic kidney disease: Univariate and multivariate analyses of factors associated with survival.

Background: Prognostic effect of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) is not fully clear yet, this study was designed to elucidate baseline characteristics of CKD patients with different severities of PH, the association between kidney indicators and PH severity, and survival factors in CKD patients with PH. Methods: We extracted clinical data from electronic medical records of all patients diagnosed with PH in CKD from Jan 2016 to Dec 2020, and those with comorbid conditions causing PH were excluded. CKD stages were defined by estimated glomerular filtration rate thresholds. PH was defined as a systolic pulmonary artery pressure (sPAP) >35 mmHg estimated using echocardiograms. Demographics, clinical data, and test results were analyzed, and all-cause mortality data were obtained. Results: A total of 137 patients were included in the study. The mean age of the participants was 60 (42.5, 67) years, the mean sPAP was 58 (51, 69.5) mmHg, and 40.9% of the patients were women. Moderate PH group had more patients undergoing dialysis and higher frequency of coronary heart disease. Moderate-severe PH group had higher parathyroid hormone levels and lower low-density lipoprotein levels. Severe PH group had better kidney function parameters and lower serum phosphorus levels. PH severity had no direct relationship with CKD stages. In the univariate analysis, age and PH severity influenced survival. Multivariate analysis also showed independent prognostic effects for age and sPAP. Kaplan-Meyer curve intuitively displayed the survival differences among CKD patients with different PH severity. Predictor values of nomogram identified from survival analyses enabled calculation of death probabilities for CKD with PH patients. Nomogram was validated by ROC analysis. Conclusions: PH begins with early-stage CKD, and PH severity is not related to CKD progression. A higher pulmonary artery pressure and an older age are associated with an increased risk of death.

Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell Apoptosis and EMT through Repressing Oxidative Stress.

Diabetic nephropathy (DN) has become the most common secondary kidney disease causing end-stage renal disease (ESRD). Nevertheless, the underlying mechanisms responsible for DN remain largely unknown. Regulated in development and DNA damage response 1 (REDD1) is a prooxidative molecule known to contribute to diabetes mellitus and its complications. However, it has not been previously examined whether and how REDD1 can further drive renal tubular epithelial cell (RTEC) apoptosis and epithelial-to-mesenchymal transition in DN. The expression of REDD1 was elevated in the kidneys of DN patients and diabetic mice in this study. By generating the DN model in REDD1 knockout mice, we demonstrated that REDD1 deficiency significantly improved apoptosis and EMT in diabetic mice. In vitro experiments showed that REDD1 generation was induced by high glucose (HG) in HK-2 cells. Similarly, the transfection of REDD1 siRNA plasmid also suppressed HG-induced apoptosis and EMT. Furthermore, we discovered that the inhibition of REDD1 suppressed the expression of Nox4-induced HG and reactive oxygen species (ROS) synthesis in HK-2 cells. In addition, HG could induce endogenous REDD1 and TXNIP to form a powerful complex. In summary, our findings demonstrate that blocking the REDD1/TXNIP complex can prevent HG-induced apoptosis and EMT by inhibiting ROS production, highlighting REDD1 as a valuable therapeutic priority site for DN.

Mycotoxins in Maize Silage from China in 2019.

Animal feed (including forage and silage) can be contaminated with mycotoxins. Here, 200 maize silage samples from around China were collected in 2019 and analyzed for regulated mycotoxins, masked mycotoxins (deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and deoxynivalenol-3-glucoside), and emerging mycotoxins (beauvericin, enniatins, moniliformin, and alternariol). Deoxynivalenol and zearalenone were detected in 99.5% and 79.5% of the samples, respectively. Other regulated mycotoxins were detected in fewer samples. The highest deoxynivalenol and zearalenone concentrations were 3600 and 830 µg/kg, respectively. The most commonly detected masked mycotoxin was 15-acetyldeoxynivalenol, which was detected in 68.5% of the samples and had median and maximum concentrations of 61.3 and 410 µg/kg, respectively. The emerging mycotoxins beauvericin, alternariol, enniatin A, enniatin B1, and moniliformin were detected in 99.5%, 85%, 80.5%, 72.5%, and 44.5%, respectively, of the samples but at low concentrations (medians <25 µg/kg). The samples tended to contain multiple mycotoxins, e.g., the correlation coefficients for the relationships between the concentrations of beauvericin and deoxynivalenol, deoxynivalenol and zearalenone, and zearalenone and beauvericin were 1.0, 0.995, and 0.995, respectively. The results indicated that there needs to be more awareness of the presence of one or more masked and emerging mycotoxins in maize silage in China.

Quantitative Transcriptomic and Proteomic Analysis of Fruit Development and Ripening in Watermelon (Citrullus lanatus).

Fruit ripening is a highly complicated process, which is modulated by phytohormones, signal regulators and environmental factors playing in an intricate network that regulates ripening-related genes expression. Although transcriptomics is an effective tool to predict protein levels, protein abundances are also extensively affected by post-transcriptional and post-translational regulations. Here, we used RNA sequencing (RNA-seq) and tandem mass tag (TMT)-based quantitative proteomics to study the comprehensive mRNA and protein expression changes during fruit development and ripening in watermelon, a non-climacteric fruit. A total of 6,226 proteins were quantified, and the large number of quantitative proteins is comparable to proteomic studies in model organisms such as Oryza sativa L. and Arabidopsis. Base on our proteome methodology, integrative analysis of the transcriptome and proteome showed that the mRNA and protein levels were poorly correlated, and the correlation coefficients decreased during fruit ripening. Proteomic results showed that proteins involved in alternative splicing and the ubiquitin proteasome pathway were dynamically expressed during ripening. Furthermore, the spliceosome and proteasome were significantly enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, suggesting that post-transcriptional and post-translational mechanisms might play important roles in regulation of fruit ripening-associated genes expression, which might account for the poor correlation between mRNAs and proteins during fruit ripening. Our comprehensive transcriptomic and proteomic data offer a valuable resource for watermelon research, and provide new insights into the molecular mechanisms underlying the complex regulatory networks of fruit ripening.

Megestrol acetate is a specific inducer of CYP3A4 mediated by human pregnane X receptor.

PURPOSE: Megestrol acetate is a synthetic progestogen used to treat some cancers and cancer-associated cachexia, but its potential interactions with other drugs are not well known. This study aims to determine the regulation of drug metabolizing enzymes by megestrol acetate. METHODS: Primary human hepatocytes were treated and analyzed by PCR array to identify genes involved in drug metabolism that are impacted by megestrol acetate. P450 3A4 (CYP3A4) reporter gene assay and HPLC analyses of nifedipine metabolites were used to determine CYP3A4 gene expression and activities. Competitive ligand binding assay was used to determine the affinity of megestrol acetate toward human pregnane x receptor (hPXR). Electrophoretic mobility shift assay and mammalian two hybrid assay were used to determine the mechanism of megestrol to activate hPXR. RESULTS: The levels and activities of CYP3A4 were significantly induced (> 4-folds) by megestrol acetate in human hepatocytes and HepG2 cells. Megestrol treatment induced CYP3A4 through the activation of hPXR, a ligand-activated transcription factor that plays a role in drug metabolism and transport. Other tested nuclear receptors showed no response. The mechanism studies showed that megestrol activated hPXR by binding to the ligand binding domain (LBD) of hPXR and increasing the recruitment of the cofactors such as steroid receptor cofactor (SRC-1). CONCLUSION: The results suggest that megestrol acetate is a specific inducer of CYP3A4 mediated by hPXR and therefore has the potential to cause drug interactions, especially in the co-administration with drugs that are substrates of CYP3A4.

Surgical Treatment Outcomes of Patients with Conus Medullaris Teratoma: A Single-Center Experience of 39 Patients.

OBJECTIVE: Conus medullaris teratomas are extremely rare, and the treatment experience has been limited. The purpose of the present study was to evaluate the clinical characteristics, radiological features, surgical outcomes, and prognosis of patients with conus medullaris teratoma. METHODS: We retrospectively reviewed the data from 39 patients who had undergone surgical resection for conus medullaris teratomas from January 2008 to December 2018. All the operations were performed by 1 senior doctor. The clinical features, pre- and postoperative magnetic resonance imaging findings, pathological features, treatment strategies, and outcomes were analyzed. The neurological status was evaluated using the modified Japanese Orthopaedic Association scale score. RESULTS: Of the 39 patients, the mean age was 30.9 years. Of the 39 patients, 20 were male and 19 were female. The symptom duration ranged from 0.3 to 252 months (mean, 61.6 months). Bladder and bowel dysfunction was the most common symptom (76.9%). Total resection was achieved in 25 patients (64.1%), subtotal resection in 11 (28.2%), and partial resection in 3 (7.7%). A mature teratoma was confirmed in all 39 patients. The neurological outcomes were improved 16 patients (45.7%), stable in 14 (40.0%), and aggravated in 5 (14.3%) at a mean follow-up of 62.7 months. Recurrence developed in 1 patient who had undergone subtotal resection. A second surgery with total resection was performed, and the patient's neurological symptoms were stable during follow-up. CONCLUSIONS: Total surgical resection is the optimal treatment strategy for patients with conus medullaris teratoma. Safe maximum tumor removal and residual tumor inactivation using electrocoagulation are recommended when total resection cannot be achieved. Surgery can provide a low recurrence rate and an acceptable low complication rate.

MicroRNA156 (miR156) Negatively Impacts Mg-Protoporphyrin IX (Mg-Proto IX) Biosynthesis and Its Plastid-Nucleus Retrograde Signaling in Apple.

Plastid-nucleus retrograde signaling (PNRS) play essential roles in regulating nuclear gene expression during plant growth and development. Excessive reactive oxygen species can trigger PNRS. We previously reported that in apple (Malus domestica Borkh.) seedlings, the expression of microRNA156 (miR156) was significantly low in the adult phase, which was accompanied by high levels of hydrogen peroxide (H2O2) accumulation in chloroplasts. However, it was unclear whether adult-phase-specific chloroplast H2O2 may induce PNRS and affect miR156 expression, or miR156 triggers adult phase PNRS during the ontogenesis. In this paper, we examined the relationship between miR156 levels and six PNRS components in juvenile and adult phase leaves from 'Zisai Pearl'×'Red Fuji' hybrids. We found that PNRS generated by singlet oxygen (1O2), the photosynthetic redox state, methylerythritol cyclodiphosphate (MEcPP), SAL1-3-phosphoadenosine 5-phosphate (PAP) and WHIRLY1 were not involved. The accumulation of Mg-protoporphyrin IX (Mg-Proto IX), the expression of the synthetic genes MdGUN5 and MdGUN6, and Mg-Proto IX PNRS related nuclear genes increased with ontogenesis. These changes were negatively correlated with miR156 expression. Manipulating Mg-Proto IX synthesis with 5-aminolevulinic acid (ALA) or gabaculine did not affect miR156 expression in vitro shoots. In contrast, modulating miR156 expression via MdGGT1 or MdMIR156a6 transgenesis led to changes in Mg-Proto IX contents and the corresponding gene expressions. It was concluded that the Mg-Proto IX PNRS was regulated downstream of miR156 regardless of adult-phase-specific plastid H2O2 accumulation. The findings may facilitate the understanding of the mechanism of ontogenesis in higher plants.

Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats.

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.

MdGGT1 Impacts Apple miR156 Precursor Levels via Ontogenetic Changes in Subcellular Glutathione Homeostasis.

The vegetative phase change in flowering plants is controlled by microRNA156 (miR156) under transcriptional regulation. However, the developmental signals upstream of miR156 are not well understood. The glutathione/glutathione disulfide (GSH/GSSG) ratios and GSH levels decline significantly during phase change, which is consistent with miR156 expression in apple (Malus domestica Borkh.). Here, we found that the content of protein conjugated glutathione was remarkably higher in chloroplasts and nuclei of adult than juvenile phase apple hybrids. The decrease in miR156 expression was most relevant to the activities of serine acetyltransferase (SAT) and soluble γ-glutamyl transpeptidase (GGT), and the expressions of MdGGT1 or MdSATs. Transgenic apples over-expressing MdMIR156 or miR156-mimetic (MIM156) did not alter MdGGT1 expression or the soluble GGT activity. Inhibition of GGT activity with serine-borate complex or acivicin led to significant reduction in GSH content, the GSH/GSSG ratio, and the expressions of MdMIR156a5, MdMIR156a12, and miR156. Depletion of GSH with diethyl maleate without altering GGT activity caused a dramatic decrease in the expression of MdMIR156a5, MdMIR156a12, and miR156. Manipulating GGT activity and GSH homeostasis by transgenic over-expressing or RNAi MdGGT1 increased or decreased MdMIR156a5 and MdMIR156a12 levels, respectively. These data provided novel evidence that MdGGT1 participates in transcriptional level of transcription regulation of miR156 precursors during ontogenesis. HIGHLIGHTS: - MdGGT1 affects thiol redox status and indirectly participates in the regulation of miR156 expression during vegetative phase change.

Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.

CO2 Diffusion in Various Carbonated Beverages: A Molecular Dynamics Study.

Carbonated beverages are widely enjoyed in spare time, yet there remain many physical and chemical processes clouded at the molecular level. In this report, we employ molecular dynamics simulations to estimate the diffusion coefficients of CO2 and the molecular origin of its variations in three model systems with characteristic features of champagnes, sugar-based cola drinks, and club sodas. The computed diffusion coefficients of CO2 are in good agreement with experimental data. Analyses of hydrogen bonding and the solvent's structural and dynamic properties reveal that the change of CO2 diffusion coefficient is closely associated with the diffusional behavior of the solvent water itself, as a result of changes in the number and strength of hydrogen bonding interactions among the species and solvent.

Fabrication of in-situ grown graphene reinforced Cu matrix composites.

Graphene/Cu composites were fabricated through a graphene in-situ grown approach, which involved ball-milling of Cu powders with PMMA as solid carbon source, in-situ growth of graphene on flaky Cu powders and vacuum hot-press sintering. SEM and TEM characterization results indicated that graphene in-situ grown on Cu powders guaranteed a homogeneous dispersion and a good combination between graphene and Cu matrix, as well as the intact structure of graphene, which was beneficial to its strengthening effect. The yield strength of 244 MPa and tensile strength of 274 MPa were achieved in the composite with 0.95 wt.% graphene, which were separately 177% and 27.4% enhancement over pure Cu. Strengthening effect of in-situ grown graphene in the matrix was contributed to load transfer and dislocation strengthening.

Characterization of cucumber violaxanthin de-epoxidase gene promoter in Arabidopsis.

Violaxanthin de-epoxidase (VDE) activates the dissipation of excessive light energy as heat and protects the photosynthetic apparatus from photo-damage. Here we quantitatively analyzed the expression characteristics of cucumber violaxanthin de-epoxidase (CsVDE) promoter using the 1983 bp upstream fragment, and a series of 5'-truncated fragments, to drive ß-glucuronidase (GUS) expression in Arabidopsis. The activity of CsVDE promoter was altered by hormones and abiotic stresses are positively by indole-3-acetic acid and gibberellin, but negatively by polyethylene glycol, abscisic acid, salicylic acid, mannitol and sodium chloride. Quantitative analysis by fluorometry of GUS activity and histochemical localization showed that the CsVDE promoter is green tissue-specific. A 334 bp fragment was sufficient to drive the expression of GUS to the same extent as the longest 1983 bp one in green tissue-specific manner. Further analysis of the promoter led to the discovery of one enhancer region and two silencer regions. The activities of GUS driven by the CsVDE promoter fragments were increased when plants were exposed to high light for 4 h, but decreased by 8 h illumination. The high light responsive elements were defined in two positions. The normal-level light-responsive elements were also found in different regions.

QM/MM through the 1990s: The First Twenty Years of Method Development and Applications.

The 2013 Nobel Prize in Chemistry was awarded to the authors of the first two publications utilizing the concept of combined quantum mechanical and molecular mechanical (QM/MM) methods. In celebrating this great event in computational chemistry, we review the early development of combined QM/MM techniques and the associated events that took place through the mid-1990s. We also offer some prospects for the future development of quantum mechanical techniques for macromolecular systems.

Diastereoselective generation of triple-stranded helicates induced by gem-dimethyl groups on a linker.

The diastereoselectivity of the self-assembly of bis(dipyrromethene) ligands with trivalent metals was improved by introducing gem-dimethyl groups to the linker.

Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters.

Chemotherapy is one of the three most common treatment modalities for cancer. However, its efficacy is limited by multidrug resistant cancer cells. Drug metabolizing enzymes (DMEs) and efflux transporters promote the metabolism, elimination, and detoxification of chemotherapeutic agents. Consequently, elevated levels of DMEs and efflux transporters reduce the therapeutic effectiveness of chemotherapeutics and, often, lead to treatment failure. Nuclear receptors, especially pregnane X receptor (PXR, NR1I2) and constitutive androstane activated receptor (CAR, NR1I3), are increasingly recognized for their role in xenobiotic metabolism and clearance as well as their role in the development of multidrug resistance (MDR) during chemotherapy. Promiscuous xenobiotic receptors, including PXR and CAR, govern the inducible expressions of a broad spectrum of target genes that encode phase I DMEs, phase II DMEs, and efflux transporters. Recent studies conducted by a number of groups, including ours, have revealed that PXR and CAR play pivotal roles in the development of MDR in various human carcinomas, including prostate, colon, ovarian, and esophageal squamous cell carcinomas. Accordingly, PXR/CAR expression levels and/or activation statuses may predict prognosis and identify the risk of drug resistance in patients subjected to chemotherapy. Further, PXR/CAR antagonists, when used in combination with existing chemotherapeutics that activate PXR/CAR, are feasible and promising options that could be utilized to overcome or, at least, attenuate MDR in cancer cells.

Structure-metabolism relationships for the glucuronidation of flavonoids by UGT1A3 and UGT1A9.

OBJECTIVES: This study tries to find structure-metabolism relationships between flavonoids and human UGT1A3 and UGT1A9. METHODS: The glucuronidation of flavonoids was studied with recombinant UGT1A3 and UGT1A9, and the glucuronidation activity was determined by HPLC. KEY FINDINGS: Of the flavonoids studied, it was shown for the first time that baicalein, quercetin-3-OCH(2) OCH(3) , quercetin-4'-CH(3) , quercetin-3'-OCH(3) and quercetin-3'-Br are substrates of UGT1A3. Wogonin, baicalein, quercetin-4'-Cl, quercetin-3-OCH(2) OCH(3) , quercetin-3-O-arabinoside, quercetin-4'-CH(3) , quercetin-3'-OCH(3) and quercetin-3'-Br are the newly reported substrates of UGT1A9. The preferred substrates for UGT1A3 and UGT1A9 contain the hydroxyl group at the C7-position. The glycon and the position of the B ring have conspicuous influences on the glucuronidation activity, and other chemical structures of flavonoids have minor effects. CONCLUSIONS: From the quantitative study, UGT1A9 in general has higher glucuronidation efficiency than UGT1A3.

The role of short-chain fatty acids in orchestrating two types of programmed cell death in colon cancer.

Short-chain fatty acids are the major by-products of bacterial fermentation of undigested fibers in the colon. SCFAs, mostly propionate and butyrate, induce differentiation, growth arrest, and apoptosis in colon cancer cells. The anticancer effect of SCFAs is also supported by epidemiological studies suggesting an inverse relationship between the level of dietary fibers and the incidence of human colon cancer. Dietary components influence the risk of human colon cancer including colon cancer through diverse mechanisms, which include the activation or inhibition of autophagy (type II programmed cell death (PCD)). Herein we demonstrate that propionate and butyrate induce autophagy in human colon cancer cells to dampen apoptosis, whereas inhibition of autophagy potentiates SCFA-induced apoptosis. The propionate-induced autophagy originates from mitochondria defects associated with cellular ATP depletion and ROS generation, both of which contribute to AMPK activation and consequential mTOR inhibition. Remarkably, when autophagy is suppressed through either pharmacological or genetic approaches, the colon cancer cells become sensitized toward propionate-induced apoptotic cell death (type I PCD). Our study is the first report characterizing this novel role of SCFAs in orchestrating two types of programmed cell death. The observed pro-survival effects of autophagy in retarding mitochondria-mediated apoptosis suggest that application of an autophagy inhibitor might improve the therapeutic efficacy of SCFAs in inducing colon cancer suppression.

G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer.

GPR43 is a G-protein-coupled receptor for short-chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N = 70) and their corresponding lymph node metastatic adenocarcinomas (N = 38). RT-PCR analysis detected the presence of full length GPR43 mRNA in only one (HT-29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin-dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA-induced cell proliferation inhibition and apoptotic cell death in colon cancer.