Melatonin inhibits tongue squamous cell carcinoma: Interplay of ER stress-induced apoptosis and autophagy with cell migration.

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and ß-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

Circular RNA in cholangiocarcinoma: A systematic review and bibliometric analysis.

BACKGROUND: Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in tumorigenesis and progression. METHODS: Four online databases (PubMed, Web of Science, Embase, and Scopus) were searched on May 04, 2023, for original papers regarding CCA and circRNAs. Bibliometric analysis of included studies was performed on R Studio and GraphPad Prism. RESULTS: Thirty studies were included in the systematic review and bibliometric analysis. The systematic review showed that circRNAs were involved in CCA proliferation, invasion, metastasis, chemotherapy resistance, and other biological processes and were related to the prognosis of patients and many clinicopathological features. Exosomal circRNAs provide a new idea for the early diagnosis of CCA. The bibliometric analysis showed a significant upward trend in the number of studies on CCA and circRNAs. The 30 included papers had 201 authors and were published in 22 English journals. The first paper was published in 2018, and the second paper was the most cited (148 citations). CONCLUSION: This systematic review and bibliometric analysis demonstrates that circRNAs in CCA have not been studied enough. CircRNAs play an important role in the occurrence and progression of CCA. They may become new targets for the diagnosis, treatment, and prognostic monitoring of CCA.

Roles of m6A modification in oral cancer (Review).

Oral cancer is one of the highly malignant tumors with poor prognosis. The pathogenic mechanisms of oral cancer have remained to be fully elucidated and this brings significant challenges to the treatment. RNA modification is a common intracellular chemical modification that has been related to various pathological processes, such as blood diseases, immune system diseases and cancer. As the most common and abundant RNA modification in eukaryotic mRNA, N6­methyladenosine (m6A) modification has a crucial role in several cancers, including oral cancer. m6A modification directly affects gene expression levels and regulates various physiological and pathological processes. It has been demonstrated that m6A modification may affect the proliferation, migration and invasion of oral cancer cells by regulating the level of m6A modification. In the present review, the effects of m6A modification on the proliferation and death of oral cancer cells, as well as the occurrence and development of oral cancer, were analyzed in order to provide a new target for treatment. Furthermore, the roles of m6A modification in chemotherapy resistance and potential immunotherapy were analyzed and new treatment ideas were provided.

Circulating levels of Elabela and Apelin in the second and third trimesters of pregnancies with gestational diabetes mellitus.

We design this study to detect levels of Elabela (ELA) and Apelin (APLN) in women with and without gestational diabetes mellitus (GDM) in the second and third trimesters, and to identify whether there is any association between ELA, APLN, and metabolic parameters. Seventy-nine GDM and 80 control subjects in the second trimester and 87 GDM and 88 healthy subjects in the third trimester were included. In the second trimester, lower ELA levels [(14.1 versus 16.9) ng/ml, p = .025] and higher APLN levels [(1021.8 versus 923.5) pg/ml, p = .046] were observed in GDM patients compared to controls. ELA levels were positively correlated with fasting plasma glucose (FPG) (r = 0.423, p < .001) in the control group, and APLN levels were negatively correlated with triglycerides (TG) (r = -0.251, p = .025) in the control group and total cholesterol (TC) (r = -0.227, p = .044) in the GDM group. ELA appeared to be related to glucose metabolism and APLN is involved in lipid metabolism during pregnancy. The expression of ELA is significantly downregulated from the second trimester to the third trimester.

Doxorubicin-loaded Cu2S/Tween-20 nanocomposites for light-triggered tumor photothermal therapy and chemotherapy.

In clinical tumor therapy, traditional treatments such as surgery, radiotherapy and chemotherapy all have their own limitations. With the development of nanotechnology, new therapeutic methods based on nanomaterials such as photothermal therapy (PTT) have also emerged. PTT takes advantage of the poor thermal tolerance of tumor cells and uses the heat generated by photothermal reagents to kill tumor cells. A transition metal sulfide represented as Cu2S is an ideal photothermal reagent because of its easy preparation, high extinction coefficient and photothermal conversion efficiency. Surface modification of nanoparticles (NPs) is also necessary, which not only can reduce toxicity and improve colloidal stability, but also can provide the possibility of further chemotherapeutic drug loading. In this work, we report the fabrication of Tween-20 (Tw20)-modified and doxorubicin (Dox)-loaded Cu2S NPs (Cu2S/Dox@Tw20 NPs), which significantly improves the performance in tumor therapy. Apart from the enhancement of colloidal stability and biocompatibility, the drug loading rate of Dox in Tw20 reaches 11.3%. Because of the loading of Dox, Cu2S/Dox@Tw20 NPs exhibit chemotherapeutic behaviors and the tumor inhibition rate is 76.2%. Further combined with a near-infrared laser, the high temperature directly leads to the apoptosis of a large number of tumor cells, while the release of chemotherapeutic drugs under heat can not only continue to kill residual tumor cells, but also inhibit tumor recurrence. Therefore, with the combination of PTT and chemotherapy, the tumor was completely eliminated. Both hematological analysis and histopathological analysis proved that our experiments are safe.

Mechanism underlying the retarded nuclear translocation of androgen receptor splice variants.

As shown in our previous study, two alternatively spliced androgen receptor (AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90 (HSP90) and importin α (the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone (DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR (Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR (Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.

Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. AIM OF THE STUDY: To investigate the chemical profiles and effects of CKF on IBS model. MATERIALS AND METHODS: The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated. RESULTS: 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d. CONCLUSIONS: CKF could alleviate the symptoms of IBS by modulating the brain-gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF.

[Analysis of bacterial diversity of kefir grains by denaturing gradient gel electrophoresis and 16S rDNA sequencing].

Kefir is an acidic, mildly alcoholic dairy beverage produced by the fermentation of milk with a grain-like starter culture. These grains usually contain a relatively stable and specific balance of microbes that exist in a complex symbiotic relationship. Kefir grains can be considered a probiotic source as it presents anti-bacterial, anti-mycotic, anti-neoplasic and immunomodulatory properties. The microorganisms in Kefir grains are currently identified by traditional methods such as growth on selective media, morphological and biochemical characteristics. However, the microorganisms that isolate by these methods can not revert to Kefir grains which indicate that there are some other bacteria that are not isolate from it. In this study, PCR-based Denaturing gradient gel electrophoresis(DGGE) and sequence analysis of 16S ribosomal RNA gene (16S rDNA) clone libraries was used for the rapid and accurate identification of microorganisms from Kefir grains. The PCR primers were designed from conserved nucleotide sequences on region V3 of 16S rDNA with GC rich clamp at the 5'-end. PCR was performed using the primers and genomic DNAs of Kefir grains bacteria. The generated region V3 of 16S rDNA fragments were separated by denaturing gel, and the dominant 16S rDNA bands were cloned, sequenced and subjected to an online similarity search. Research has shown that regions V3 of 16S rDNAs have eight evident bands on the DGGE gel. The sequence analysis of these eight bands has indicated that they belong to different four genera, among them three sequences are similar to Sphingobacterium sp. whose similarities with database sequences are over 98%, three sequences are similar to Lactobacillus sp. whose similarities with database sequences are over 96%, the other two sequence are similar to Enterobacter sp., and Acinetobacter sp. whose similarities with database sequences are over 99% respectively. Although the DGGE method may have a lower sensitivity than the ordinary PCR methods, because when universal bacterial PCR primers are used, only the dominant microbiota of an ecosystem will be visualized on a DGGE gel, producing complex banding patterns. However, it could visualize the bacterial qualitative compositions and reveal the major species of the Kefir grains. Among them Sphingobacterium can be found in Kefir grains as the predominant flora which is reported for the first time. PCR-based DGGE and sequence analysis of 16S rDNA proved to be a valuable culture-independent approach for the rapid and specific identification of the microbial species present in microecosystem and probiotic products.