Spatiotemporal Dynamics in the Burden of Lip and Oral Cavity Cancer and Attributable Risk Factors in Asia (1990-2021).

Lip and oral cavity cancer (LOC) remains a critical public health challenge in Asia. This study evaluated spatiotemporal trends and risk factor contributions to LOC-related disability-adjusted life years (DALYs) from 1990 to 2021 to inform evidence-based healthcare policies. Using Global Burden of Disease (GBD) 2021 data, we analyzed LOC DALYs stratified by age, gender, risk factors (smoking, alcohol use, tobacco chewing), and subregions in Asia.

Global, regional, and national burden of disease analysis on paralytic ileus and intestinal obstruction in adults aged 65 and over from 1990 to 2021, with projections for 2030: a Global Burden of Disease Study 2021 analysis.

Objective: This study aimed to evaluate the burden and trends of paralytic ileus and bowel obstruction in individuals aged ≥ 65 years, offering insights into prevention, treatment, and healthcare policy.

Methods: Data from the Global Burden of Disease Study 2021 were used to analyze paralytic ileus and intestinal obstruction by demographics, year, country/region, and Socio-Demographic Index (SDI). The statistical methods included Joinpoint regression, decomposition analysis, and Bayesian Age-Period-Cohort modeling.

β-ecdysone/PLGA composite scaffolds promote skull defect healing in diabetic rat.

Introduction: Diabetes mellitus often leads to bone metabolism disorders, hindering bone regeneration and delaying the healing of bone defects. β-Ecdysone, a plant-derived hormone known for its wide range of physiological activities, possesses hypoglycemic effects and promotes osteogenic differentiation. This study developed a composite PLGA slow-release scaffold loaded with β-ecdysone to enhance its bioavailability through topical administration and to investigate its potential to heal diabetic bone defects.

Cxcl10 is required for survival during SARS-CoV-2 infection in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide ~5 years since the first documented case. Severe COVID-19 is widely considered to be caused by a dysregulated immune response to SARS-CoV-2 within the respiratory tract. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in pathogenesis and its suitability as a therapeutic target have remained undefined.

Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2.

The Caenorhabditis elegans 12-kDa small heat shock proteins with little in vitro chaperone activity play crucial roles for its dauer formation, longevity, and reproduction.

Small heat shock proteins (sHSPs) are known to exhibit in vitro chaperone activity by suppressing the aggregation of misfolded proteins. The 12-kDa sHSPs (Hsp12s) subfamily members from Caenorhabditis elegans, including Hsp12.2, Hsp12.

The tRNA-like small noncoding RNA mascRNA promotes global protein translation.

mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown.

High-fat diet triggers obesity-related early infiltration of macrophages into adipose tissue and transient reduction of blood monocyte count.

Infiltration of adipose tissue macrophages (ATMs) is a typical feature of obesity, and circulating immune cells may indicate immune cell accumulation. However, it remains unclear whether this is true in the early stages of obesity. This study aimed to define the role of blood monocytes in obesity and the relationship between blood monocytes and ATMs in early-stage obesity.

Mitochondrial Trafficking and Processing of Telomerase RNA TERC.

Mitochondrial dysfunctions play major roles in many diseases. However, how mitochondrial stresses are relayed to downstream responses remains unclear. Here we show that the RNA component of mammalian telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol.

Redox-responsive F127-folate/F127-disulfide bond-d-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors.

Introduction: The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR).

Materials And Methods: This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond-d-α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and d-α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity.

Mammalian mitochondrial RNAs are degraded in the mitochondrial intermembrane space by RNASET2.

Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood.

Effects of a Mutation in the Gene Encoding the Mitochondrial Co-chaperonin HSP10 and Its Potential Association with a Neurological and Developmental Disorder.

We here report molecular investigations of a missense mutation in the gene encoding the HSP10 subunit of the HSP60/ HSP10 chaperonin complex that assists protein folding in the mitochondrial matrix. The mutation was identified in an infant who came to clinical attention due to infantile spasms at 3 months of age. Clinical exome sequencing revealed heterozygosity for a NM_002157.

Kinetically-defined component actions in gene repression.

Gene repression by transcription factors, and glucocorticoid receptors (GR) in particular, is a critical, but poorly understood, physiological response. Among the many unresolved questions is the difference between GR regulated induction and repression, and whether transcription cofactor action is the same in both. Because activity classifications based on changes in gene product level are mechanistically uninformative, we present a theory for gene repression in which the mechanisms of factor action are defined kinetically and are consistent for both gene repression and induction.

A novel mechanism for small heat shock proteins to function as molecular chaperones.

Small heat shock proteins (sHSPs) are molecular chaperones ubiquitously present in all forms of life, but their function mechanisms remain controversial. Here we show by cryo-electron microscopy and single particle 3D reconstruction that, at the low temperatures (4-25°C), CeHSP17 (a sHSP from Caenorhabditis elegans) exists as a 24-subunit spherical oligomer with tetrahedral symmetry. Our studies demonstrate that CeHSP17 forms large sheet-like super-molecular assemblies (SMAs) at the high temperatures (45-60°C), and such SMAs are apparently the form that exhibits chaperone-like activity.

A kinase-independent activity of Cdk9 modulates glucocorticoid receptor-mediated gene induction.

A gene induction competition assay has recently uncovered new inhibitory activities of two transcriptional cofactors, NELF-A and NELF-B, in glucocorticoid-regulated transactivation. NELF-A and -B are also components of the NELF complex, which participates in RNA polymerase II pausing shortly after the initiation of gene transcription. We therefore asked if cofactors (Cdk9 and ELL) best known to affect paused polymerase could reverse the effects of NELF-A and -B.

A conserved protein motif is required for full modulatory activity of negative elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor-regulated gene induction properties.

NELF-B is a BRCA1-interacting protein and subunit (with NELF-A, -C/D, and -E) of the human negative elongation factor (NELF) complex, which participates in RNA polymerase II pausing shortly after transcription initiation, especially for synchronized gene expression. We now report new activities of NELF-B and other NELF complex subunits, which are to attenuate glucocorticoid receptor (GR)-mediated gene induction, reduce the partial agonist activity of an antagonist, and increase the EC50 of an agonist during nonsynchronized expression of exogenous and endogenous reporters. Stable knockdown of endogenous NELF-B has the opposite effects on an exogenous gene.

Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice.

Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa.

Synthesis, receptor binding, and CNS pharmacological studies of new thyrotropin-releasing hormone (TRH) analogues.

As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes.

Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging.

Background: Obesity is a hallmark of aging in many Western societies, and is a precursor to numerous serious age-related diseases. Ghrelin (Ghrl), via its receptor (growth hormone secretagogue receptor, GHS-R), is shown to stimulate GH secretion and appetite. Surprisingly, our previous studies showed that Ghrl(-/-) mice have impaired thermoregulatory responses to cold and fasting stresses, while Ghsr(-/-) mice are adaptive.

The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells.

The extracellular calcium-sensing receptor (CaSR) has recently been recognized as an L-amino acid sensor and has been implicated in mediating cholecystokinin (CCK) secretion in response to aromatic amino acids. We investigated whether direct detection of L-phenylalanine (L-Phe) by CaSR results in CCK secretion in the native I cell. Fluorescence-activated cell sorting of duodenal I cells from CCK-enhanced green fluorescent protein (eGFP) transgenic mice demonstrated CaSR gene expression.

A stem cell marker-expressing subset of enteroendocrine cells resides at the crypt base in the small intestine.

The spatial orientation of the enteroendocrine cells along the crypt-villus axis is closely associated with their differentiation in the intestine. Here we studied this relationship using primary duodenal crypts and an ex vivo organoid system established from cholecystokinin-green fluorescent protein (CCK-GFP) transgenic mice. In the primary duodenal crypts, GFP+ cells were found not only in the upper crypt but also at the crypt base, where the stem cells reside.

Effects of technetium-99 methylenediphosphonate on cytokine-induced activation of retro-ocular fibroblasts from patients with Graves' ophthalmopathy.

Objective: To explore the effects of technetium-99 methylenediphosphonate (99Tc-MDP) on cell proliferation, hyaluronic acid (HA) synthesis and the expressions of human leucocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1) on cultured retro-ocular fibroblasts (RFs) from patients with Graves' ophthalmopathy.

Methods: After two to seven passages, cultured RFs were incubated for 72 h with interferon-γ (100 U/ml), interleukin-1 (100 U/ml) or tumour necrosis factor-α (100 U/ml) in the presence of 99Tc-MDP. Flow cytometry was used to investigate the expression of HLA-DR and ICAM-1.

The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin.

Background & Aims: Long-chain fatty acid receptors G-protein-coupled receptor 40 (GPR40) (FFAR1) and GPR120 have been implicated in the chemosensation of dietary fats. I cells in the intestine secrete cholecystokinin (CCK), a peptide hormone that stimulates digestion of fat and protein, but these cells are rare and hard to identify. We sought to determine whether dietary fat-induced secretion of CCK is directly mediated by GPR40 expressed on I cells.

Giant vesicle formation through self-assembly of chitooligosaccharide-based graft copolymers.

A simple approach is described for the preparation of chitooligosaccharide-based giant vesicles with variable size by simply tuning the water content in the water-dioxane mixture, by which reactive vesicles with diameters in the range of 0.5-400 microm were easily prepared.