Explorative case control study on the associations of serum vitamin D3, folic acid and vitamin B12 levels on Kawasaki disease and coronary artery lesions.

Background: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs). Methods: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups. Results: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size. Conclusion: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

The analysis of inducible family members in the water flea Daphnia magna led to the identification of an uncharacterized lineage of heat shock protein 70.

To explore the function and evolutionary relationships of inducible heat shock protein 70 (Hsp70) in Daphnia magna, cDNAs of four Hsp70 family members (DmaHsp70, DmaHsp70-2, DmaHsp70-12, DmaHsp70-14) were cloned. While all DmaHsp70s possess three function domains, it is noteworthy that only DmaHsp70 ends with a "EEVD" motif. Phylogenetic analysis indicates that the Hsp70-12 lineage is distanced from the rest, and therefore it is an uncharacterized lineage of Hsp70. The differences in isoelectric point and 3-dimensional (3D) conformation of the N-terminal nucleotide binding domain (NBD) of DmaHsp70s further support the theory. DmaHsp70s exhibit varied motif distribution patterns and the logo sequences of motifs have diverse signature characteristics, indicating that different mechanisms are involved in the regulation of ATP binding and hydrolysis for the DmaHsp70s. Protein-protein network together with the predicted subcellular locations of DmaHsp70s suggest that they likely fulfill distinct roles in cells. The transcription of four DmaHsp70s were changed during the recovery stage after thermal stress or oxidative stress. But the expression pattern of them were dissimilar. Collectively, these results collectively elucidated the identification of a previously uncharacterizedHsp70 lineage in animal and extended our understanding of the Hsp70 family.

Correction to: The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma.

The authors would like to correct figure, as the error was introduced in the preparation of this figure for publication. We sincerely apologize for having this error in the article, the authors have provided corrected version of figure here.

Cisplatin-induced senescence in ovarian cancer cells is mediated by GRP78.

Glucose-regulated protein 78 (GRP78), the most abundant and well-characterized glucose-regulated protein, is a major stress-inducible chaperone localized to the endoplasmic reticulum (ER). The purpose of the present study was to investigate the mechanisms of GRP78 involved in the senescence sensitivity of ovarian cancer cells to cisplatin. In the present study, we found that the chemotherapy-sensitive ovarian tumor sections showed strong staining for heterochromatin protein 1-γ (HP1-γ), but weak staining for GRP78. Cisplatin-sensitive A2780 cells with low expression of GRP78 tended to undergo senescence easily when compared with the cisplatin-resistant C13K cells following a dose-gradient cisplatin exposure. Forced overexpression of GRP78 protected the cisplatin-sensitive A2780 cells from cisplatin-induced senescence through P53 and CDC2. Knockdown of GRP78 rescued the senescence sensitivity of cisplatin-resistant C13K cells to cisplatin through P21 and CDC2. Twisting of Ca2+ release from ER stores by GRP78 was established to be associated with the sensitivity of cisplatin-induced senescence in ovarian cancer cell lines. In conclusion, GRP78 may have anti-senescence effects on ovarian cancer cells involving multiple mechanisms. Intervention against GRP78 may reduce cisplatin resistance in ovarian cancer.

Triggering of death receptor apoptotic signaling by human papillomavirus 16 E2 protein in cervical cancer cell lines is mediated by interaction with c-FLIP.

Human papillomavirus (HPV) E2 gene disruption is one of the key features of HPV-induced cervical malignant transformation. Though it is thought to prevent progression of carcinogenesis, the pro-apoptotic function of E2 protein remains poorly understood. This study shows that expression of HPV16 E2 induces apoptosis both in HPV-positive and -negative cervical cancer cell lines and leads to hyperactivation of caspase-8 and caspase-3. Activation of these signaling factors is responsible for the observed sensitivity to apoptosis upon treatment with anti-Fas antibody or TNF-α. In addition, immunoprecipitation experiments clearly show an interaction between HPV16 E2 and c-FLIP, a key regulator of apoptotic cell death mediated by death receptor signaling. Moreover, c-FLIP and a caspase-8 inhibitor protect cells from HPV16 E2-mediated apoptosis. Overexpression of c-FLIP rescues cervical cancer cells from apoptosis induced by HPV16 E2 protein expression. The data suggest that HPV16 E2 abrogates the apoptosis-inhibitory function of c-FLIP and renders the cell hypersensitive to the Fas/FasL apoptotic signal even below threshold concentration. This suggests a novel mechanism for deregulation of cervical epithelial cell growth upon HPV-induced transformation, which is of great significance in developing therapeutic strategies for intervention of cervical carcinogenesis.

The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma.

PURPOSE: Integration of high-risk human papillomavirus (HR-HPVs) into the host DNA has been proposed as a risk for cervical carcinogenesis. HPV-16 is the predominant high-risk type and its integration ration varied largely in different cervical cancer (CC) samples. The aim of this study was to evaluate the correlation between physical state of HPV16 infection and extent of cervical lesion, as well as the clinical significance of virus existing state. METHODS: A total of 252 cases of paraffin-embedded blocks derived from cancer precursor lesion and cervical carcinoma samples were detected by HC-II for HR-HPV infection. HPV16 infection was confirmed by PCR and immunohistochemistry for HPV16 E7 simultaneously. The physical state of HPV16 infection were assessed by PCR for 3 overlapping fragments in E2 gene and multiple PCR for E2 gene and E7 gene. RESULTS: The infection ratio of HR-HPV in normal cervical tissue, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cervical cancer were 15.0, 32.8, 54.3, 69.7, 93.8%, respectively. HR-HPV positive samples of 62.8% were infected with HPV16. The integration ratio of HPV16 in CIN III and cervical carcinoma were 35.7 and 58.1% respectively, both of which were significantly higher than that of CIN I and normal cervical tissues. The discrepancy was statistically significant (P < 0.05). Furthermore, it was observed that persistent virus infection and progression of cervical lesion were more common in CIN I with integrated HPV16 than that with episomal HPV16. CONCLUSION: The integration ratio of HPV16 was accompanied by an increase in the grade of cervical lesion. The integrated state of HPV16 infection was strongly associated with persistent HPV infection and progression of cervical lesions.