Epidemiology and antifungal susceptibilities of clinically isolated Aspergillus species in South China.

Aspergillosis is a rising concern worldwide; however, its prevalence is not well documented in China. This retrospective study determined Aspergillus's epidemiology and antifungal susceptibilities at Meizhou People's Hospital, South China. From 2017 to 2022, the demographic, clinical, and laboratory data about aspergillosis were collected from the hospital's records and analysed using descriptive statistics, chi-square test, and ANOVA. Of 474 aspergillosis cases, A. fumigatus (75.32%) was the most common, followed by A. niger (9.92%), A. flavus (8.86%), and A. terreus (5.91%). A 5.94-fold increase in aspergillosis occurred during the study duration, with the highest cases reported from the intensive care unit (52.74%) - chronic pulmonary aspergillosis (79.1%) and isolated from sputum (62.93%). Only 38 (8.02%) patients used immunosuppressant drugs, while gastroenteritis (5.7%), haematologic malignancy (4.22%), and cardiovascular disease (4.22%) were the most prevalent underlying illnesses. In A. fumigatus, the wild-type (WT) isolates against amphotericin B (99.1%) were higher than triazoles (97-98%), whereas, in non-fumigatus Aspergillus species, the triazole (95-100%) WT proportion was greater than amphotericin B (91-95%). Additionally, there were significantly fewer WT A. fumigatus isolates for itraconazole and posaconazole in outpatients than inpatients. These findings may aid in better understanding and management of aspergillosis in the region.

Six-Year Retrospective Analysis of Epidemiology, Risk Factors, and Antifungal Susceptibilities of Candidiasis from a Tertiary Care Hospital in South China.

Candidiasis is a life-threatening disease that increases mortality in critically ill patients. However, such epidemiological data are still lacking in underdeveloped regions of China. A retrospective analysis (2016 to 2021) was conducted in Meizhou People's Hospital, China to study the burden of candidiasis, particularly candidemia, and antifungal susceptibilities of the species among hospitalized patients. Of the 7,864 candidiasis cases, 461 (5.86%) were candidemia cases. Candida albicans (64.25%) was the most identified species, followed by C. tropicalis (12.61%), C. glabrata (10.79%), and C. parapsilosis (9.79%). In non-C. albicans (NCA) candidemia cases, the number of C. glabrata cases was higher (102/461, 22.37%) than C. tropicalis (64/461, 14.04%). Gastrointestinal pathology, respiratory dysfunctions, septic shock, and malignancies were common underlying comorbidities, respectively. A central venous catheter was an independent risk factor for both C. albicans and NCA candidemia. The mortality rate was not statistically significant for either C. albicans or NCA. Amphotericin B and 5-flucytosine were highly effective (98 to 100%), while azoles were least effective (67.74 to 95.66%). Candidemia cases caused by C. tropicalis and C. glabrata had significantly lower azole susceptibility than non-candidemia-causing isolates. This study provides valuable information for prescribers to choose the right empirical therapy, for researchers to explore different resistance mechanisms, and for health care managers to control candidiasis better. IMPORTANCE This study provides important information on the burden of candidiasis, particularly candidemia, and the antifungal susceptibility of Candida species among hospitalized patients in an underdeveloped region of China. First, the finding that azoles were least effective against Candida species causing candidemia is particularly noteworthy, as it suggests the possibility of resistance to this class of antifungal agents. This information can guide the choice of empirical therapy and help in the selection of appropriate antifungal agents for the treatment of candidemia, thereby reducing the risk of resistance development. Second, the study provides important information for researchers to explore different resistance mechanisms in Candida species. Finally, the study has important implications for health care managers in controlling the spread of candidiasis. The high prevalence of candidemia cases in the study highlights the need for appropriate infection control measures to prevent the spread of the disease.

miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by targeting forkhead box O1.

AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Many microRNAs (miRNAs), small non-coding RNAs, are involved in regulating cancer cell proliferation, metastasis, migration, invasion and apoptosis. MAIN METHODS: We investigated the expression of miR-135a in HCC cell lines and clinical tissues. The effect of miR-135a on migration and invasion of HepG2 and MHCC-97L were examined using wound healing and Transwell assay. We determined the expression of miR-135a, forkhead box O1 (FOXO1), matrix metalloproteinase-2 (MMP-2) and Snail using real-time PCR and western blotting. KEY FINDINGS: We found miR-135a was upregulated in HCC cell lines and tissues. miR-135a overexpression promoted HCC cells migration and invasion, whereas miR-135a inhibition suppressed HCC cells migration and invasion. miR-135a overexpression could upregulate the expression of MMP2, Snail and the phosphorylation of AKT, but decreased FOXO3a phosporylation. Tumor suppressor FOXO1 was the direct target for miR-135a. SIGNIFICANCE: Our results suggested that miR-135a might play an important role in promoting migration and invasion in HCC and presents a novel mechanism of miRNA-mediated direct suppression of FOXO1 in HCC cells.

LIM protein JUB promotes epithelial-mesenchymal transition in colorectal cancer.

Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.