The Role of Nuclear Phosphoinositides in the p53-MDM2 Nexus.

Recent insights into the p53-MDM2 nexus have advanced deeper understanding of their regulation and potent impact on cancer heterogeneity. The roles of nuclear phosphoinositide (PIPs) in modulating this pathway are emerging as a key mechanism. Here, we dissect the molecular mechanisms by which nuclear PIPs stabilize p53 through the recruitment of small heat shock proteins (sHSPs), activate the nuclear phosphatidylinositol 3-kinase (PI3K)-AKT signaling cascade, and modulate MDM2 function to regulate the p53-MDM2 interaction.

Inhalable liposomal delivery of osimertinib and DNA for treating primary and metastasis lung cancer.

Lung cancer remains one of the most common malignancies, and its brain metastases significantly worsen the prognosis for patients. Current treatments for lung cancer face many challenges, including poor drug accumulation and the inability to simultaneously control primary and metastatic tumors. Here, we show that the mRNA-binding protein insulin-like growth factor 3 is crucial for non-small cell lung cancer progression and metastasis.

ZIF-8-Modified Multifunctional Hydrogel Loading siRNA and DOX for Postoperative Therapy of Maxillofacial Osteosarcoma and Bone Repair.

The primary clinical challenges associated with postoperative maxillofacial osteosarcoma include high mortality rates and significant local recurrence. Additionally, patients often exhibit substantial bone defects that are incapable of self-healing, necessitating the implantation of scaffolds. Multifunctional hydrogels, which enable sustained local release of therapeutic agents and enhance scaffold surface properties, demonstrate significant potential for the postoperative management of maxillofacial osteosarcoma.

A study on the treatment of rheumatoid arthritis with lipid nanoparticles containing mRNA encoding heat shock protein 10.

In order to delay the progression of Rheumatoid Arthritis (RA) in patients, and to prevent further teratogenesis and irreversible bone erosion through drug intervention in the early stages of inflammation, this experiment used the mRNA encoding heat shock protein 10 (HSP10) (H-mRNA) as the main therapeutic drug and used Microfluidics technology to prepare lipid nanoparticles (LNP) (H-mRNA LNPs) containing H-mRNA, and the surface of H-mRNA-LNPs was modified using heparin particals to obtain the final formulation H-mRNA-LNPs @ heparin/ Protamine. Through the sequence modification and effect evaluation of H-mRNA, we explored the formulation screening, physical characterization, cytotoxicity in vitro, distribution in vivo, pharmacodynamics in vivo, and safety in vivo of the prepared lipid nanoparticles, which proved that this nano-preparation had good anti Rheumatoid Arthritis effects, and conducted a preliminary exploration for the application of nucleic acid drugs in the treatment of diseases outside of tumors. This research would provide new ideas for the treatment of RA.

Preparation and release pattern study of long-term controlled release Blonanserin microspheres.

To prepare a PLGA microsphere loaded with the antipsychotic Blonanserin without release leg period and released in a near-zero model for long time, in this study, 15 kDa and 75 kDa PLGA were chosen to be mixed with different ratios, and Blonanserin microspheres (Bn-MS) without significant differences in the particle size, drug loading capacity, and encapsulation rate were prepared by microfluidics. The release kinetic model was fitted to the release behavior by monitoring the changes in particle size and morphology during the Bn-MS release to investigate microspheres' in vitro release pattern. The results showed that the addition of appropriate ratios of mixed molecular weights to Bn-MS could eliminate the release hysteresis period.

Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation.

Local injection of anti-inflammatory drugs for osteoarthritis emerged as a promising administration in the clinic, and sustained-release dosage forms have great potential for future therapeutic applications. Controlling the response of patients only in the acute inflammatory phase is currently the focus of therapeutic interventions. To relieve acute pain in patients and to improve the long-term prognosis effect of osteoarthritis treatment, we designed a two-pronged approach in this research: an injectable double-layer microsphere containing a "nonsteroidal anti-inflammatory drug - macrophage polarizing factor" was constructed.

Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application.

Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.

Beneficial or detrimental: Recruiting more types of benign cases for cancer diagnosis based on salivary glycopatterns.

With the advantages of convenient, painless and non-invasive collection, saliva holds great promise as a valuable biomarker source for cancer detection, pathological assessment and therapeutic monitoring. Salivary glycopatterns have shown significant potential for cancer screening in recent years. However, the understanding of benign lesions at non-cancerous sites in cancer diagnosis has been overlooked.

TGF-β1 Triggers Salivary Hypofunction via Attenuating Protein Secretion and AQP5 Expression in Human Submandibular Gland Cells.

Aging-related salivary gland degeneration usually causes poor oral health. Periductal fibrosis frequently occurs in the submandibular gland of the elderly. Transforming growth factor β1 (TGF-β1) is the primary driving factor for fibrosis, which exhibits an increase in the fibrotic submandibular gland tissue.

Choroidal Circulation in 8- to 30-Year-Old Chinese, Measured by SS-OCT/OCTA: Relations to Age, Axial Length, and Choroidal Thickness.

Purpose: The purpose of this study was to evaluate and explore the determinants of choroidal vascularity and choriocapillaris perfusion in a Chinese population aged 8 to 30 years old.

Methods: Three hundred eighty eyes from 380 subjects aged 8 to 30 years were included in this cross-sectional study. Submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and choriocapillaris flow deficit (CcFD) were estimated using images obtained from optical coherence tomography (OCT).

Mutual regulation between glycosylation and transforming growth factor-β isoforms signaling pathway.

Transforming growth factor-beta (TGF-β) superfamily members orchestrate a wide breadth of biological processes. Through Sma and Mad (Smad)-related dependent or noncanonical pathways, TGF-β members involve in the occurrence and development of many diseases such as cancers, fibrosis, autoimmune diseases, cardiovascular diseases and brain diseases. Glycosylation is one kind of the most common posttranslational modifications on proteins or lipids.

Advances in IgA glycosylation and its correlation with diseases.

Immunoglobulin A (IgA) is the most abundant immunoglobulin synthesized in the human body. It has the highest concentration in the mucosa and is second only to IgG in serum. IgA plays an important role in mucosal immunity, and is the predominant antibody used to protect the mucosal surface from pathogens invasion and to maintain the homeostasis of intestinal flora.

High Expression Level of α2-3-Linked Sialic Acids on Salivary Glycoproteins of Breastfeeding Women May Help to Protect Them from Avian Influenza Virus Infection.

Terminal sialic acids (Sia) on soluble glycoprotein of saliva play an important role in the clearance of influenza virus. The aim of this study is to investigate the alteration of sialylation on the salivary proteins of women during the lactation period and its effect on the saliva binding ability to virus. In total, 210 saliva samples from postpartum women with and without breastfeeding were collected, and the expression level of α2-3/6-linked Sia on the whole salivary proteins and specific glycoproteins of IgA and MUC5B from different groups were tested and verified using lectin microarray, blotting analysis and ELISA based method.

Differences in Retinal and Choroidal Vasculature and Perfusion Related to Axial Length in Pediatric Anisomyopes.

Purpose: The purpose of this study was to evaluate the interocular differences in choroidal vasculature, choriocapillaris perfusion, and retinal microvascular network, and to explore their associations with interocular asymmetry in axial lengths (ALs) in children with anisomyopia.

Methods: Refractive error, AL, and other biometric parameters were measured in 70 children with anisomyopia. Using optical coherence tomography (OCT) and OCT-angiography, we measured the submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD), retinal vessel density (VD), and foveal avascular zone (FAZ) area.

Pregnancy-associated decrease of Siaα2-3Gal-linked glycans on salivary glycoproteins affects their binding ability to avian influenza virus.

Salivary glycoproteins are known as an important barrier to inhibit influenza infection by presenting sialic acid (Sia) ligands that can bind with viral hemagglutination. Here, to further understand why pregnant women are more vulnerable to avian influenza virus (AIV), we investigated the alteration of protein sialylation in the saliva of women during pregnancy and postpartum, and its impact on the saliva binding affinity to AIV. Totally 1200 saliva samples were collected, the expression levels of terminal α2-3/6-linked Sia on salivary proteins were tested and validated, and the binding activities of salivary proteins were assessed against 3 strains of AIV and the H1N1 vaccine.