Single-stranded circular RNAs (circRNAs), generated through 'backsplicing', occur more extensively than initially anticipated. The possible functions of the vast majority of circRNAs remain unknown. ...Virus-derived circRNAs have recently been described in gamma-herpesviruses. We report that oncogenic human papillomaviruses (HPVs) generate circRNAs, some of which encompass the E7 oncogene (circE7). HPV16 circE7 is detectable by both inverse RT-PCR and northern blotting of HPV16-transformed cells. CircE7 is N
-methyladenosine (m
A) modified, preferentially localized to the cytoplasm, associated with polysomes, and translated to produce E7 oncoprotein. Specific disruption of circE7 in CaSki cervical carcinoma cells reduces E7 protein levels and inhibits cancer cell growth both in vitro and in tumor xenografts. CircE7 is present in TCGA RNA-Seq data from HPV-positive cancers and in cell lines with only episomal HPVs. These results provide evidence that virus-derived, protein-encoding circular RNAs are biologically functional and linked to the transforming properties of some HPV.
Protein kinase C has been implicated in the phosphorylation of the erythrocyte/brain glucose transporter, GLUT1, without a clear understanding of the site(s) of phosphorylation and the possible ...effects on glucose transport. Through in vitro kinase assays, mass spectrometry, and phosphospecific antibodies, we identify serine 226 in GLUT1 as a PKC phosphorylation site. Phosphorylation of S226 is required for the rapid increase in glucose uptake and enhanced cell surface localization of GLUT1 induced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Endogenous GLUT1 is phosphorylated on S226 in primary endothelial cells in response to TPA or VEGF. Several naturally occurring, pathogenic mutations that cause GLUT1 deficiency syndrome disrupt this PKC phosphomotif, impair the phosphorylation of S226 in vitro, and block TPA-mediated increases in glucose uptake. We demonstrate that the phosphorylation of GLUT1 on S226 regulates glucose transport and propose that this modification is important in the physiological regulation of glucose transport.
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•PKC phosphorylates GLUT1 on S226 in vitro and in vivo in endothelial cells•TPA-induced, rapid increases in glucose uptake require S226 phosphorylation•Phosphorylation of S226 increases GLUT1 membrane localization•Some GLUT1 deficiency syndrome mutations show impaired S226 phosphorylation
The functional significance of GLUT1 phosphorylation by PKC is unclear. Lee et al. identify a phosphorylation site, demonstrate its essential role in the rapid induction of glucose uptake, and find that its phosphorylation is impaired by mutations that cause GLUT1 deficiency syndrome.
Proliferating cells, compared with quiescent cells, are more dependent on glucose for their growth. Although glucose transport in keratinocytes is mediated largely by the Glut1 facilitative ...transporter, we found that keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, thus suggesting metabolic adaptation. However, cultured Glut1-deficient keratinocytes displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation decreased hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also decreased inflammation in these models. Glut1 inhibition decreased the expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis.
Cancer is the greatest disease burden in Korea. Cancer screening can reduce the burden of cancer but cancer screening rates among Koreans remain low. The purposes of this study were to a) understand ...Koreans' beliefs and knowledge about cancer screening, and b) explore preferred strategies for increasing cancer screening utilization.
We conducted a descriptive, qualitative study using eight face-to-face focus groups with a total of 64 Koreans aged 40 and over. Participants answered semi-structured, open-ended questions assessing their experiences with, and beliefs, knowledge, and opinions about, cancer screening. All interview data were recorded and analyzed in the context of the health belief model (HBM).
The most important themes that emerged from the focus group data were (a) perceived susceptibility (most of the participants believed they were not susceptible to cancer; those who perceived themselves susceptible to cancer were reluctant to express it); (b) perceived benefits (early detection and feelings of relief after cancer screening were benefits; participants had screening because they wanted to take advantage of the Korean government's Medical Payment Support program for cancer patients who have participated in the National Cancer Screening program); (c) perceived barriers (no symptoms; self-care when having symptoms; widespread distrust of tests, doctors, and hospitals; unkind health care providers; the financial burdens of advanced cancer screening tests; and the discomfort during cancer screening); and (d) knowledge of the causes of cancer (incorrect knowledge including beliefs that stress, personality, and body overuse cause cancer). Almost all of the participants were very knowledgeable about the seriousness of cancer and were confident that they were able to have cancer screening. Participants preferred strategies of cancer screening using group interventions with family or friends; various information delivery methods; information emphasizing the importance of cancer prevention; convenient, free, or inexpensive services; and kind health care providers.
This HBM-based research suggests that beliefs in low susceptibility to cancer, many barriers to cancer screening, and incorrect knowledge should be the foci for increasing cancer screening rates in Koreans. Interventions could change individual cultural beliefs and increase knowledge as well as the quality of health care for Koreans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human ...polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
The purpose of this study was to describe the experiences of Korean family caregivers of patients with cancer by reviewing recent literature.
Methods
Five electronic databases were ...searched—MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PubMed for English literature, and Korean Information Service System (KISS), and Research Information Sharing Service (RISS) for Korean literature for articles published from January 2010 to March 2020 using the key words cancer, caregiver, and Korean. Twenty‐six articles met the inclusion criteria and remained in the final review.
Results
No intervention study was found and most of studies were quantitative without theoretical/conceptual framework. All the studies were conducted with Koreans living in Korea. No previous study has been conducted with Koreans living in the U.S. or other countries. Most studies focused on caregivers' quality of life, burden, unmet needs, and resilience/adaptation/post‐traumatic growth.
Conclusions
Comprehensive intervention studies focused on improving quality of life, burden, and adaptation to their complex roles as caregivers in the context of Korean culture would be helpful. Further research is needed in examining the caregiver‐patient dyad interactions longitudinally to understand the dynamic complicated processes of caregiving.
The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased ...after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.
Background Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective We determined ...whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods We screened biopsy specimens showing “peacock plumage” histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. Results We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. Limitation This was a small case series of archived materials. Conclusion We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as “HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses.”
BACKGROUND:Studies on colorectal cancer (CRC) screening among Korean Americans (KAs) lack culturally sensitive, reliable, and validated belief scales.
OBJECTIVE:The purpose of this study was to ...adapt, modify, and validate instruments measuring cultural beliefs (physical space, health temporal orientation, personal control, colon cancer fatalism, and health fatalism) about CRC screening in KAs.
METHODS:In phase I, instrument adaptation and modification (translation from English into Korean, individual interviews using cognitive interviewing, and expert reviews) were used to make existing cultural beliefs instruments culturally appropriate for KAs. In phase II, instrument validation (pilot test and cross-sectional survey) was used to examine the psychometric properties of the instrument among 202 KAs.
RESULTS:Construct validity and reliability of the final Korean version of the instruments were examined using exploratory and confirmatory factor analyses and internal consistency reliability. Exploratory factor analysis using all of the cultural beliefs items resulted in 5 factors accounting for 46.55% of the variance. Factor loadings were greater than 0.40 for most items to be added to the scales reflecting Korean cultural perspectives. Cronbach’s αs for all the cultural beliefs subscales were greater than .70.
CONCLUSIONS:Findings from this study show that KAs have unique cultural beliefs that should be reflected in the instruments used for CRC screening research with this population.
IMPLICATIONS FOR PRACTICE:The revised instrument could be useful in accurately measuring cultural beliefs among KAs and in developing culturally sensitive interventions to increase CRC screening behaviors among KAs.
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