Mushroom Poisoning Outbreaks - China, 2023.

What is already known about this topic?: Mushroom poisoning poses a significant food safety concern in China, with a total of 196 species identified in poisoning incidents by the end of 2022. What is added by this report?: In 2023, the China CDC conducted an investigation into 505 cases of mushroom poisoning spanning 24 provincial-level administrative divisions. This investigation resulted in 1,303 patients and 16 deaths, yielding a case fatality rate of 1.23%. A total of 97 mushrooms were identified as the cause of 6 distinct clinical disease types, with 12 species newly documented as poisonous mushrooms in China. What are the implications for public health practice?: Close collaboration among CDC staff, physicians, and mycologists remains crucial for the control and prevention of mushroom poisoning in the future.

Altered brain function in patients with acrophobia: A voxel-wise degree centrality analysis.

AIM: To explore the local spontaneous neural activity and whole-brain functional connectivity patterns in the resting brain of acrophobia patients. METHODS: 50 patients with acrophobia and 47 healthy controls were selected for this study. All participants underwent resting-state MRI scans after enrollment. The imaging data were then analyzed using a voxel-based degree centrality (DC) method, and seed-based functional connectivity (FC) correlation analysis was used to explore the correlation between abnormal functional connectivity and clinical symptom scales in acrophobia. The severity of symptoms was evaluated using self-report and behavioral measures. RESULTS: Compared to controls, acrophobia patients showed higher DC in the right cuneus and left middle occipital gyrus and significantly lower DC in the right cerebellum and left orbitofrontal cortex (p < 0.01, GRF corrected). Additionally, there were negative correlations between the acrophobia questionnaire avoidance (AQ- Avoidance) scores and right cerebellum-left perirhinal cortex FC (r = -0.317, p = 0.025) and between scores of the 7-item generalized anxiety disorder scale and left middle occipital gyrus-right cuneus FC (r = -0.379, p = 0.007). In the acrophobia group, there was a positive correlation between behavioral avoidance scale and right cerebellum-right cuneus FC (r = 0.377, p = 0.007). CONCLUSIONS: The findings indicated that there are local abnormalities in spontaneous neural activity and functional connectivity in the visual cortex, cerebellum, and orbitofrontal cortex in patients with acrophobia.

Mushroom Poisoning Outbreaks - China, 2022.

What is already known about this topic?: Mushroom poisoning is one of the most serious food safety issues in China. By the end of 2021, over 520 poisonous mushrooms had been discovered in China. The Southwest region of China was the most severely affected. Mushroom poisonings mainly concentrated in the summer and autumn months. What is added by this report?: In 2022, China CDC conducted an investigation of 482 incidents of mushroom poisoning across 21 provincial-level administrative divisions (PLADs). This resulted in 1,332 patients and 28 deaths, with a total case fatality rate of 2.1%. A total of 98 mushrooms were identified, causing 7 different clinical types of diseases. Three provisional new species (Collybia humida nom. prov., Spodocybe venenata nom. prov., and Omphalotus yunnanensis nom. prov.) were newly recorded as poisonous mushrooms in China, in addition to 10 other species. What are the implications for public health practice?: In view of the extensive impact and harm of poisonous mushrooms on public health, it is necessary to promote prevention and improve the ability of professionals to identify, diagnose, and treat mushroom poisoning.

Mushroom Poisoning Outbreaks - China, 2021.

What is already known about this topic?: Mushroom poisoning is one of the most serious food safety issues in China. Most poisoning incidents resulted from eating mushrooms causing gastroenteritis and psycho-neurological disorder from which patients usually could fully recover. Most deaths resulted from species causing acute liver failure and rhabdomyolysis, and the remaining deaths were attributed to acute renal failure and hemolysis. What is added by this report?: In 2021, the total number of investigations was 327 from 25 provincial-level administrative divisions, involving 923 patients and 20 deaths, and the overall mortality was 2.17%. Overall, 74 poisonous mushrooms causing 6 different clinical syndromes were successfully identified, 15 of which were newly recorded in China as poisonous mushrooms. What are the implications for public health practice?: Considering the potential huge risks for collecting and eating wild mushrooms, we strongly advise not collecting and eating unfamiliar wild mushrooms. Promoting knowledge about poisonous mushrooms is essential and urgent to reduce mushroom poisonings. Precise species identification timely after mushroom poisoning is important for appropriate diagnosis and treatment. Many deaths were ascribed to delayed hospitalization.

Mushroom Poisoning Outbreaks - China, 2020.

SUMMARY: What is already known about this topic? Acute liver failure, rhabdomyolysis, acute renal failure, and hemolysis caused by poisonous mushrooms are the most important mushroom poisoning threats to the Chinese population. The most notorious lethal mushrooms are the species from genera Amanita, Lepiota, and Galerina that cause acute liver failure, and Russula subnigricans that leads to rhabdomyolysis.What is added by this report? In 2020, the total number of investigations reached 676, involving an estimated 102 species of poisonous mushrooms, 24 of which were newly recorded in China. Gyromitra venenata was newly discovered in incidents in Yunnan and Guizhou provinces and were the first reported poisonings due to gyromitrins in China since 2000. The rare poisoning Shiitake mushroom dermatitis was recorded in China. Hemolysis poisoning caused by Paxillus involutus was recorded for the second time since the beginning of the new century, resulting in one death in Inner Mongolia Autonomous Region.What are the implications for public health practice? Promoting knowledge about safe consumption of mushrooms is essential to reduce mushroom poisonings. It is not wise to collect and eat wild mushrooms. For southwestern provinces such as Yunnan, especially, caution must be exercised with unfamiliar mushroom species.

Mushroom Poisoning Outbreaks - China, 2019.

What is already known about this topic? Mushroom poisoning is becoming one of the most serious food safety issues in China, which is responsible for nearly a half of all oral poisoning deaths. What is added by this report? In China, many mushrooms were previously "recorded" as poisonous. In this study, about 70 species obtained from mushroom poisoning incidents including several new records were confirmed accurately by morphological and molecular evidence in 2019, and spatial and temporal distribution characters of 13 lethal mushrooms were summarized systematically. What are the implications for public health practice? Precise and timely species identification is of pivotal importance in mushroom incidents. More efforts and cooperation are continued to be needed urgently for the governments, CDC staff, doctors and mycologists in future.

A Foodborne Bongkrekic Acid Poisoning Incident - Heilongjiang Province, 2020.

What is already known on this topic? Poisoning incidents caused by bongkrekic acid (BA), one of the metabolites of Burkholderia gladioli pathovar cocovenenans (B. cocovenenans), have been reported in Indonesia, Mozambique, and China. The reported case fatality rates averaged 60%, 32%, and 26.5%, respectively. In China, B. cocovenenans is often called Pseudomonas cocovenenans subsp. farinofermentans. What is added by this report? In October 2020, 9 persons in Jidong County, Heilongjiang Province died after consuming a homemade fermented corn flour product - sour soup - with a case fatality rate of 100%. BA was detected in both food samples and biological samples with a content of 330 mg/kg and 3 mg/L, respectively. The doses of BA consumed by the cases were approximately 22-33 times the lethal dose in human. What are the implications for public health practice? The consumption of fermented corn flour products, deteriorated fresh tremella, or black fungus and metamorphic starch products may cause BA poisoning. Health education should be strengthened so that homemade-starch-fermented food should be avoided and foods that have been kept for a long time should not be consumed. Meanwhile, training and emergency capacity building for primary healthcare workers should be strengthened to provide timely diagnosis and response.

Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.

Successful implantation of an embryo requires adequate depth of invasion in the endometrium, which depends upon decidualization. The aim of the present study was to elucidate why humans experience spontaneous decidualization and menstruation while most other mammals do not. We established a spontaneous decidualization model in pseudopregnant rats with vitamin E deficiency (VED) to investigate mechanisms associated with spontaneous decidualization. Vaginal smears were used to monitor bleeding while vitamin E levels were analyzed with a commercial vitamin E assay kit. Trypan blue staining was used to observe the implantation site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5, and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles of pseudopregnancy. Vitamin E levels in the VED group were markedly lower compared to the control group in both the plasma and uterus, while the level of vitamin E in the liver did not differ between the control and VED groups. Spontaneous decidualization in the VED group was validated by histological examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the VED group was more than twice that of the control group. The mean total anti-oxidizing capability, catalase level, and glutathione peroxidase activity were significantly reduced in the decidualized portion of the VED group compared to controls, while the malondialdehyde level was also significantly higher in the decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5 dpc and increasing levels of reactive oxygen species are responsible for spontaneous decidualization in VED rats.

The Rho GTPase RhoE is a p53-regulated candidate tumor suppressor in cancer cells.

Previous studies have shown that RhoE, an atypical member of the Rho GTPase family, may play an opposite role to RhoA in regulating cell proliferation and invasion. To explore the relationship between RhoE and the malignant phenotypes of human cancer, we have determined the expression patterns of RhoE in varying grade of human cancer tissues and tested the effects of RhoE expression in several RhoE underexpressing cancer cell lines. Systemic immunocytochemistry analyses of gastric, colorectal, lung and breast carcinomas, respectively, showed that RhoE protein expression was significantly decreased in most cancer cases compared with that of adjacent normal tissues. Enhanced RhoE expression could markedly inhibit proliferation, migration and invasion and induce apoptosis of the cancer cells which have relatively low levels of endogenous RhoE expression. Wild-type p53 (wt-p53) could strongly increase RhoE expression in p53-transfected cells. Furthermore, the luciferase assays indicated that wt-p53 significantly enhanced the activities of RhoE promoter compared with mutant p53 (mt-p53) in PC3 cells (p53 null). Collectively, data are presented showing that RhoE may participate in human cancer progression and act as a candidate target of p53, and these findings also strongly suggest that RhoE may be a new candidate tumor suppressor and could serve as a potential target in the gene therapy of cancer.

miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells.

It has become increasingly clear that microRNAs play an important role in many human diseases including cancer. Here, we show that expression of miR-21 in HEK293 and several colorectal cancer cells was found inversely correlated with ras homolog gene family, member B (RhoB) expression. miR-21 expression significantly suppressed RhoB 3' UTR luciferase-reporter activity, but the inhibitory effect was lost when the putative target sites were mutated. Exogenous miR-21 over-expression mimicked the effect of RhoB knockdown in promoting proliferation and invasion and inhibiting apoptosis, whereas anti-miR-21 or RhoB expression yielded opposite effects, in colorectal cancer cells. These results suggest that miR-21 is a regulator of RhoB expression and RhoB could be a useful target in exploring the potential therapeutic benefits of miR-21 mediated tumor cell behaviors in colorectal cancer.

[Analysis of gene expression patterns in an irinotecan-resistance colon cancer cell by cDNA microarray].

OBJECTIVE: To study the mechanism of irinotecan-resistant colon cancer by analyzing the differential gene expression patterns with cDNA microarray. METHODS: Total RNA was purified from irinotecan-sensitive colonic cancer cell line, SW480 and its irinotecan-resistance cell line, SW480/CPT. The cRNA retro-transcribed from RNA were labeled with Cy3 fluorescence as probes. The probes were hybridized with Agilent gene chips and the fluorescence images of the chips were obtained with Axon 4000B scanner as well as analyzed with Genepix 3.0 software. The microarray results were confirmed by reverse transcription-polymerase chain reaction. RESULTS: Of the 1598 genes with altered expressions, there were 911 up-regulated genes and 687 down-regulated genes. Glutathione S-Transferase (GST) isoenzyme family GSTA such as GSTA1, GSTA2, GSTA3 and GSTA5 were significantly up-regulated. The expression levels of many Zinc finger protein family members (ZNF) were also differentially regulated. CONCLUSION: GSTA and ZNF subunit genes might play an important regulation role in the irinotecan resistance of colon cancer.

Epigenetic modification of RhoE expression in gastric cancer cells.

RhoE is a unique member of Rho family of GTPases without detectable intrinsic GTPase activity. Our previous study showed that RhoE is a tumor suppressor gene and its expression is down-regulated in gastric cancer. However, the mechanism underlying the down-regulated expression of RhoE in gastric cancer has not been elucidated yet. In the present study, the effect of epigenetic modification on the RhoE expression in gastric cancer cells was investigated. The mRNA and protein expression of RhoE were detected by real-time RT-PCR and Western blotting, respectively. Results showed RhoE was significantly down-regulated in three gastric cancer cell lines. A promoter (2980 bp) of RhoE and its five truncated mutants were cloned into vector pGL-3Basic for the activity analysis by luciferase reporter assay. Treatment with trichostatin A, a histone deacetylation inhibitor, enhanced not only the activity of RhoE promoter, but also the mRNA and protein expression of RhoE in three gastric cancer cell lines, whereas treatment with 5-Aza-2'-deoxycytidine, a DNA methylation inhibitor, affected neither RhoE promoter activity nor RhoE expression. No synergistic effect was observed in cells treated with both drugs. Our results suggested that RhoE expression in gastric cancer cells was regulated by histone deacetylation, but not by DNA methylation, at the epigenetic level.

miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells.

Increasing evidence in the past few years has shown that miRNAs could serve functionally as "oncogenes" or "tumor suppressor genes" and regulate multiple cellular processes relevant to carcinogenesis and cancer progression. Both RhoA and Cdc42, two members of the Rho GTPase family, are found to be upregulated in several types of human tumors including colorectal cancer, and have been implicated in cancer initiation and progression. In the present studies, we found that miR-185 expression greatly inhibited the proliferation potential of Hela cells. An examination of the predicted targets of miR-185 revealed RhoA and Cdc42 among the putative targets that are crucial for cell proliferation. A genomic sequence analysis indicated that nt 1844-1852 of the RhoA 3'UTR and nt 1382-1396 of the cdc42 3'UTR encode for miR-185 target matching sequences and they are highly conserved across different species. Using a luciferase-reporter assay, we show that miR-185 expression significantly suppressed the RhoA and Cdc42 3'UTR activities, and the inhibitory effect was lost when the putative target sites for miR-185 were mutated. Consistent with these results, ectopic expression of miR-185 reduced protein levels of RhoA and Cdc42 in cells, indicating miR-185 functionally regulates RhoA and Cdc42 abundance. Similar to the effects of knocking down RhoA and/or Cdc42 expression, miR-185 effectively inhibited proliferation, induced G1 cell cycle arrest and apoptosis, and blocked invasion of colorectal cancer cells. Thus, miR-185 is a negative regulator of RhoA and Cdc42 and their cellular activities, and could inhibit proliferation and invasion of colorectal cancer cells.

miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells.

miRNAs have emerged as post-transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Cdc42, one of the best characterized members of the Rho GTPase family, is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. In the present study, we have identified miR-137 as a potential regulator of Cdc42 expression. A bioinformatics search revealed a putative target-site for miR-137 within the Cdc42 3' UTR at nt 792-798, which is highly conserved across different species. Expression of miR-137 in colorectal cancer cell lines was found inversely correlated with Cdc42 expression. miR-137 could significantly suppress Cdc42 3' UTR luciferase-reporter activity, and this effect was not detectable when the putative 3' UTR target-site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced both mRNA and protein expression levels of Cdc42 and mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest, and blocking invasion of the colorectal cancer cells, whereas anti-miR-137 expression led to the opposite effect. Furthermore, expression of miR-137 suppressed the immediate downstream effector of Cdc42, PAK signaling. Our results suggest that miR-137 may have a tumor suppressor function by directly targeting Cdc42 to inhibit the proliferation and invasion activities of colorectal cancer cells. They raise an interesting possibility that Cdc42 activity and function can be controlled by miRNAs in addition to the classic regulators such as guanine nucleotide exchange factors and GTPase-activating proteins.

Establishment and biological characteristics of oxaliplatin-resistant human colon cancer cell lines.

BACKGROUND AND OBJECTIVE: Chemotherapy is the main treatment for colon cancer, while multidrug-resistance is the main reason for chemotherapy failure and tumor relapse. This study was to establish two oxaliplatin-resistant colon cancer cell lines and evaluate their biological characteristics. METHODS: Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin (L-OHP) of low and gradually increased concentration. Growth curve, cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay. The expressions of P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1) and MRP2 were detected by Western blot. Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry. RESULTS: It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin. Cross-resistance to 5-fluorouracil, etoposide, cisplatin, vincristine and epirubicin but not to paclitaxel was observed. Longer doubling time, higher proportion of cells in G(0)/G(1) phase and lower proportion in G(2)/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines. The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated, while those of P-gp and MRP1 had no significant change. CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells. CONCLUSIONS: SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.

Effects of microRNA-29 family members on proliferation and invasion of gastric cancer cell lines.

BACKGROUND AND OBJECTIVE: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in the biologic behavior of cells. This study was designed to investigate the effect of members of the microRNA-29 family on the expression of cell division cycle 42 (Cdc42) and their roles on proliferation, migration, and invasion of gastric cancer cells. METHODS: We detected microRNA-29s and Cdc42 expression in gastric cancer cells by real-time polymerase chain reaction (PCR) and Western blot analysis. Negative controlled RNA (ncontrol), microRNA-29 family members (microRNA-29a, -29b, and -29c), and Cdc42-specific small interfering RNA (si-Cdc42) were chemically synthesized and transfected into SGC7901 and BGC823 gastric cancer cells, which have a relatively low expression of microRNA-29s and a relatively high expression of Cdc42. The expression of Cdc42 and the phosphorylation of its downstream molecular PAK1 expressions were determined by Western bolt analysis. Cell Counting Kit-8 was used to measure cell proliferation, and wound-healing and invasion assays were used to examine the abilities of migration and invasion. RESULTS: Similar to si-Cdc42, the ectopic expression of microRNA-29 family members significantly reduced the expression of Cdc42 and its downstream molecular PAK1 phosphorylation levels. Consistently, ectopic expression of microRNA-29s inhibited proliferation and migration in gastric cancer cells. Invasive cell counts of the SGC7901, ncontrol/SGC7901, si-Cdc42/SGC7901, microRNA-29a/SGC7901, microRNA-29b/SGC7901, and microRNA-29c/SGC7901 cell groups were 84.0+/-4.2, 71.7+/-4.6, 16.3+/-3.2, 15.7+/-3.8, 16.3+/-3.0, and 16.7+/-3.1, respectively. The invasive cell counts of the BGC823, ncontrol/BGC823, si-Cdc42/BGC823, microRNA-29a/BGC823, microRNA-29b/BGC823, and microRNA-29c/BGC823 cell groups were 199.0+/-10.5, 146.3+/-9.7, 72.7+/-8.2, 86.7+/-8.5, 86.0+/-8.5, and 73.3+/-8.3, respectively (P<0.05). CONCLUSIONS: Members of the microRNA-29 family can obviously inhibit cell proliferation, migration, and invasion of gastric cancer cells by targeting Cdc42.