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Abstract Background Primary brain and central nervous system cancer (collectively called CNS cancers) cause a significant burden to society. The purpose of this study was to evaluate the trends in the burden of CNS cancers from 1990 to 2019 and to predict the incidence and mortality rates and the corresponding numbers for the next 25 years to help countries to understand the trends in its incidence and mortality, and to make better adjustments or formulation of policies and allocation of resources thereby reducing the burden of the disease. Methods The 2019 Global Burden of Disease Study provided incidence rates, death rates, and disability-adjusted life year (DALY) data in Asia from 1990 to 2019. To reflect the trends in the age-standardized incidence, mortality, and DALY rates, the estimated annual percentage change (EAPC) was determined. The Bayesian age-period cohort (BAPC) model was employed to predict the burden of CNS cancers in the next 25 years. Results The incidence, death, and DALY rates of CNS cancers all increased from 1990 to 2019. The age-standardized incidence rate (ASIR) for CNS cancers increased from 9.89/100,000 in 1990 to 12.14/100,000 in 2019, with an EAPC of 0.69 (95% confidence interval (CI): 0.65, 0.73). The ASDR and the age-standardized DALY rate both decreased, with EAPCs of − 0.08 and − 0.52, respectively. Before 2005, the age-standardized DALY rate in East Asia was much greater in females than in males, while in Central Asia, the age-standardized death and DALY rates in males both increased sharply after 2000. In contrast to 1990, the caseload increased for the 55–70 years age group. The number of deaths decreased sharply among individuals aged younger than 20 years, especially in East Asia, accounting for only 5.41% of all deaths. The age group with the highest mortality rate was > 60 years, especially in Japan. The ASIR will continue to increase in Asia from 2020 to 2044, and the ASDR will gradually diminish. The incidence and number of deaths from CNS cancers in Asia are expected to increase over the next 25 years, especially among females. Conclusions The study identified an increasing trend in morbidity, mortality and disability-adjusted life-years (DALYs), with differences in age-standardized morbidity rates for different population groups. In addition, it is noteworthy that the burden of disease (as measured by disability-adjusted life-years (DALYs)) is higher among women in Central Asia compared with other regions. ASIR will continue to increase over the next 25 years, with the increase in female cases and mortality expected to be more pronounced. This may need to be further substantiated by additional research, on the basis of which health authorities and policymakers can better utilize limited resources and develop appropriate policies and preventive measures.

Abstract Background The cadherin-4 gene (CDH4), a member of the cadherin family genes, encodes R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. The function of CDH4 in OSCC (oral squamous cell carcinoma) is unknown. Materials and methods We use the Cancer Genome Atlas (TCGA) database to find the expression of CDH4 in OSCC is more than normal tissue. Our tissue samples also confirmed that CDH4 gene was highly expressed in OSCC. The related cell function assay detected that CDH4 promotes the ability of cell proliferation, migration, self-renewal and invasion. Cell staining experiment confirmed that the change of CDH4 expression would change the cell mortality. The western blot of GPX4 (glutathione-dependent peroxidase-4), GSH (reduced glutathione) test assay and MDA(Malondialdehyde) test assay show that the expression of CDH4 may resist the sensitivity of ferropotosis in OSCC. Results CDH4 was upregulated in OSCC samples and was correlation with poor survival of patients. High expression of CDH4 effectively promotes the proliferation, mobility of OSCC cells and reduce the sensitivity of OSCC cells to ferroptosis. CDH4 is positively correlated with EMT pathway genes, negatively correlated with fatty acid metabolism pathway genes and peroxisome pathway genes, and positively correlated with ferroptosis suppressor genes in OSCC. Conclusions These results indicate that CDH4 may play a positive role in tumor progression and resistance ferroptosis and may be a potential therapeutic target for OSCC.

C11H12O4, monoclinic, P21 (no. 4), a = 15.4586(2) Å, b = 7.80238(13) Å, c = 16.4003(2) Å, β = 91.0103(13)°, V = 1977.81(5) Å3, Z = 8, Rgt(F) = 0.0413, wRref(F2) = 0.1045, T = 180 K.

ObjectiveTo study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding trends among five sociodemographic index regions, 21 regions, and 204 countries for decision-making, which would enable policymakers to distribute limited resources and devise policies more rationally.MethodsData on uterine fibroids (UNs) from 1990 to 2019, including incidence, mortality, and DALYs, were obtained from the 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated to assess morbidity, mortality, and DALY trends.ResultsThe incident cases of UFs increased from 5,769,658 (95%UI, 7,634,3995–4,274,824) incidences in 1990 to 9,643,336 (95%UI, 7,178,053-12,714,741) incidences in 2017, and the age-standardized incidence rate was steady at 225.67/100,000 persons (95%UI, 167.33–298.87) in 1990 to 241.18/100,000 persons (95%UI, 179,45–318.02) in 2019. The incidence ratio in the high sociodemographic index (SDI) region showed a unimodal distribution, with peaks in 2005. Between 2009 and 2017, the age-standardized death rate of UFs declined globally, especially in low-SDI and low-middle SDI regions. In contrast with 860,619 DALYs (95%UI, 473,067-1,505,289) in 1990, the number of DALYs was 1,378,497 (95%UI, 710,915-2,475,244) in 2019, which had increased significantly, whereas the age-standardized DALY rate decreased expressively with an EAPC of −1.93 (95%CI, from −2.16 to −1.71).ConclusionThe global burden of UFs increased between 1990 and 2019, and the incidences and DALYs increased prominently worldwide, while the deaths from UFs had no evident growth. Lower SDI regions carried an incremental burden of UFs, while disease reduction was observed in higher SDI regions. It is high time we paid attention to the underprivileged regional quality of life and health protection.

Abstract Background Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC. Methods Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion. Results We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed. Conclusions The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC.

Cryotherapy is a common non-pharmacological method to relieve pain and inflammation. Clinical studies have shown that cryotherapy can reduce postoperative pain after root canal therapy, but the mechanism remains unclear. In this study, we aimed to investigate the underlying molecular mechanisms by which cryotherapy reduces inflammation in lipopolysaccharide (LPS)-stimulated periodontal ligament cells through transcriptome sequencing analysis. We found that cryotherapy significantly reduced the expression of multiple proinflammatory cytokines and chemokines, and NFKB1 was the key regulator down-regulated by cryotherapy. Importantly, we discovered that lncRNA SNHG1 expression level significantly decreased after cold treatment. SNHG1 expression was positively related to NFKB1 while negatively correlated with miR-9-5p, which formed a novel ceRNA regulatory pathway. Knockdown of SNHG1 significantly reduced the expression of NFKB1, IL1B, and IL6, while overexpression of SNHG1 significantly increased the expression of these genes. In conclusion, our study demonstrated that cryotherapy can effectively reduce inflammation in LPS-induced periodontal ligament cells by suppressing the lncRNA SNHG1/miR-9-5p/NFKB1 axis. [ABSTRACT FROM AUTHOR]

As1the most revolutionary technology in cell therapy, stem cell technology will give birth to a series of new biotechnology, drive the development of the pharmaceutical industry, and lead the future of biological economy. Guangdong province has a good foundation for stem cell R&D and has set up a project named "Stem Cell and Tissue Engineering Technology" to make breakthroughs in core technologies of stem cell research. In this paper, it is of great significance to compile the industrial technology roadmap and clarify the key points of stem cell and tissue engineering industry through the research to provide reference for the decision-making in Guangdong province.

Ki67 is a well-known proliferation marker with a large size of around 350 kDa, but its biological function remains largely unknown. The roles of Ki67 in tumor prognosis are still controversial. Ki67 has two isoforms generated by alternative splicing of exon 7. The roles and regulatory mechanisms of Ki67 isoforms in tumor progression are not clear. In the present study, we surprisingly find that the increased inclusion of Ki67 exon 7, not total Ki67 expression level, was significantly associated with poor prognosis in multiple cancer types, including head and neck squamous cell carcinoma (HNSCC). Importantly, the Ki67 exon 7-included isoform is required for HNSCC cell proliferation, cell cycle progression, cell migration, and tumorigenesis. Unexpectedly, Ki67 exon 7-included isoform is positively associated with intracellular reactive oxygen species (ROS) level. Mechanically, splicing factor SRSF3 could promote exon 7 inclusion via its two exonic splicing enhancers. RNA-seq revealed that aldo-keto reductase AKR1C2 is a novel tumor-suppressive gene targeted by Ki67 exon 7-included isoform in HNSCC cells. Our study illuminates that the inclusion of Ki67 exon 7 has important prognostic value in cancers and is essential for tumorigenesis. Our study also suggested a new SRSF3/Ki67/AKR1C2 regulatory axis during HNSCC tumor progression. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with a nucleophosmin 1 (NPM1) mutation is a unique subtype of adult leukemia. Recent studies show that NPM1-mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in NPM1-mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated m6A modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of NPM1-mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.

Regulatory T (Treg) cells play crucial roles in maintaining immune self-tolerance and immune homeostasis, and closely associated with many human diseases. Recently, Treg cells-derived extracellular vesicles (Treg-EVs) have been demonstrated as a novel cell-contact independent inhibitory mechanism of Treg cells. Treg-EVs contain many specific biological molecules, which are delivered to target cells and modulate immune responses by inhibiting T cell proliferation, inducing T cell apoptosis, and changing the cytokine expression profiles of target cells. The abnormal quantity or function of Treg-EVs is associated with several types of human diseases or conditions, such as transplant rejection, inflammatory diseases, autoimmune diseases, and cancers. Treg-EVs are promising novel potential targets for disease diagnosis, therapy, and drug transport. Moreover, Treg-EVs possess distinct advantages over Treg cell-based immunotherapies. However, the therapeutic potential of Treg-EVs is limited by some factors, such as the standardized protocol for isolation and purification, large scale production, and drug loading efficiency. In this review, we systematically describe the structure, components, functions, and basic mechanisms of action of Treg-EVs and discuss the emerging roles in pathogenesis and the potential application of Treg-EVs in human diseases. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations exhibits distinct biological and clinical features, accounting for approximately one-third of AML. Recently, the N 6-methyladenosine (m6A) RNA modification has emerged as a new epigenetic modification to contribute to tumorigenesis and development. However, there is limited knowledge on the role of m6A modifications in NPM1-mutated AML. In this study, the decreased m6A level was first detected and high expression of fat mass and obesity-associated protein (FTO) was responsible for the m6A suppression in NPM1-mutated AML. FTO upregulation was partially induced by NPM1 mutation type A (NPM1-mA) through impeding the proteasome pathway. Importantly, FTO promoted leukemic cell survival by facilitating cell cycle and inhibiting cell apoptosis. Mechanistic investigations demonstrated that FTO depended on its m6A RNA demethylase activity to activate PDGFRB/ERK signaling axis. Our findings indicate that FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated AML and provide a new layer of epigenetic insight for future treatments of this distinctly leukemic entity. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) carrying nucleophosmin (NPM1) mutations has been defined as a distinct entity of acute leukaemia. Despite remarkable improvements in diagnosis and treatment, the long‐term outcomes for this entity remain unsatisfactory. Emerging evidence suggests that leukaemia, similar to other malignant diseases, employs various mechanisms to evade killing by immune cells. However, the mechanism of immune escape in NPM1‐mutated AML remains unknown. In this study, both serum and leukemic cells from patients with NPM1‐mutated AML impaired the immune function of CD8+ T cells in a co‐culture system. Mechanistically, leukemic cells secreted miR‐19a‐3p into the tumour microenvironment (TME) via small extracellular vesicles (sEVs), which was controlled by the NPM1‐mutated protein/CCCTC‐binding factor (CTCF)/poly (A)‐binding protein cytoplasmic 1 (PABPC1) signalling axis. sEV‐related miR‐19a‐3p was internalized by CD8+ T cells and directly repressed the expression of solute‐carrier family 6 member 8 (SLC6A8; a creatine‐specific transporter) to inhibit creatine import. Decreased creatine levels can reduce ATP production and impair CD8+ T cell immune function, leading to immune escape by leukemic cells. In summary, leukemic cell‐derived sEV‐related miR‐19a‐3p confers immunosuppression to CD8+ T cells by targeting SLC6A8‐mediated creatine import, indicating that sEV‐related miR‐19a‐3p might be a promising therapeutic target for NPM1‐mutated AML. [ABSTRACT FROM AUTHOR]

C11H12O4, monoclinic, P21 (no. 4), a = 15.4586(2) Å, b = 7.80238(13) Å, c = 16.4003(2) Å, β = 91.0103(13)°, V = 1977.81(5) Å3, Z = 8, Rgt(F) = 0.0413, wRref(F2) = 0.1045, T = 180 K. [ABSTRACT FROM AUTHOR]

C11H12O4, monoclinic, P21 (no. 4), a = 15.4586(2) Å, b = 7.80238(13) Å, c = 16.4003(2) Å, β = 91.0103(13)°, V = 1977.81(5) Å3, Z = 8, Rgt(F) = 0.0413, wRref(F2) = 0.1045, T = 180 K. [ABSTRACT FROM AUTHOR]