Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective To evaluate the effect of photo-activated disinfection(PAD)as a kind of adjuvant treatment on moderate to severe chronic periodontitis.Methods 21 patients with the chronic periodontitis(totally 218 selected sites)were randomly enrolled and divided into group A(minocycline hydrochloride),group B(PAD),group C(PAD + minocycline hydrochloride),and group D(no adjunctive therapy)for the adjunctive treatment after receiving the scaling and root planing(SRP).Periodontal indexs as probing depth(PD),bleeding on probing(BOP)and clinical attachment loss(CAL)were examined at the baseline,6 and 12 weeks after the treatment.Meanwhile,periodontal pathogens as Porphyromonas gingivalis(Pg)and Tannerella forsythia(Tf)from subgingival plaque of group A,B and C were detected by Real-time PCR.Results Compared with the baseline,the periodontal inflammations of all groups were improved signiffcantly at 6 and 12 weeks after the treatment(P<0.001),and group A,group B and group C were better than group D(P<0.001),group C was better than group A(P<0.001);Furthermore,the concentration of Pg and Tf was decreased significantly(P<0.001),and there was no difference among the three groups with adjunctive therapy.Conclussion As the adjunctive treatment of SRP,PAD could achieve the same and even better effect than minocycline hydrochloride ointment.

BACKGROUND:Among the surface modification technologies of metal implants,micro-arc oxidation has been widely concerned for its convenience,low cost and ability to effectively adjust the microstructure and elements of surface coatings. OBJECTIVE:To summarize research advances in physical and chemical properties and biological activities of oxidation coatings prepared by micro-arc oxidation on different materials. METHODS:The articles about the effects of micro-arc oxidation on the biological activity of medical metals were searched in PubMed and Web of Science based on the English search terms"MAO,micro-arc oxidation,osseointegration,mechanical property,biological activity,angiogenesis,fibrogenesis".The search time was from January 2016 to December 2022.According to the inclusion and exclusion criteria,82 articles were finally retained for review. RESULTS AND CONCLUSION:Micro-arc oxidation is a potential surface modification technology,which can greatly improve the success rate of implantation,and can be widely used in other fields.The specific reasons are as follows:(1)Micro-arc oxidation technology forms special porous morphology on the surface of materials,which can optimize the mechanical properties such as wear resistance and corrosion resistance,contributing to the reduction of the degradation rate of magnesium alloys.(2)Micro-arc oxidation technology can significantly enhance the bioactivity and improve the bioinertness of titanium and titanium alloys through the addition of strontium,hydroxyapatite and other metallic or nonmetallic substances to its porous morphology for helping elevate its osteogenic differentiation,angiogenesis,fibrogenesis and other biological activities.

BACKGROUND:Micro-arc oxidation can effectively add bioactive elements to the metal surface and improve the anti-bacterial and anti-inflammatory properties of biomedical metal materials,so this technology has become one of the hotspots of biomedical materials. OBJECTIVE:To summarize the anti-bacterial and anti-inflammatory properties of surface coatings prepared by the combination of micro-arc oxidation and other surface modification technologies. METHODS:Articles from January 1996 to December 2022 were searched on CNKI,WanFang and PubMed databases using Chinese and English search terms"micro-arc oxidation,antibacterial properties,anti-inflammatory properties,metal implants".After preliminary screening according to inclusion and exclusion criteria,89 articles were retained and summarized. RESULTS AND CONCLUSION:The ceramic layer prepared by micro-arc oxidation can improve the anti-bacterial and anti-inflammatory properties of titanium,magnesium and other alloys.Combination with other surface modification technologies can effectively solve the effect of pores on the surface properties of the alloy,and further improve the biological properties of the oxide film.It has a wide application prospect in orthopedics and dentistry.At present,most studies are limited to metal coatings,and most of them focus on metal elements with good antibacterial properties such as silver and copper,while only a few studies mention non-metallic coatings such as graphene oxide,hydroxyapatite and chitosan.In the future,extensive studies can be conducted on inorganic coatings and polymer coatings,and more combinations of different bioactive elements can also be adopted to improve antibacterial properties.Currently,studies on the inflammation of implant coatings prepared by micro-arc oxidation are mostly limited to the immune system and focused on macrophages,while studies on neutrophils and platelets are scarce.In the future,a variety of advanced technologies should be combined to explore the specific effects of micro-arc oxidation coating on other immune cells and inflammatory cells.

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9％, and the relative error accuracy (RE) ranged from -0.5％-2.0％. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

Objective: To analyze the clinical response in cases of multi-victims bitten by a dog in Beijing (one of whom was HIV positive), and to explore the route and prognosis of dual exposure to rabies virus and HIV. Methods: Descriptive epidemiological methods were used to analyze the exposed cases, the post-exposure prophylaxis(PEP) of rabies and HIV and the follow-up outcomes. Results: After six months-follow up, there was no rabies case was found among those nine victims bitten by the suspected dog. In addition, six HIV-negative victims who had been exposed to HIV via dog saliva were consistently tested to be HIV negative in the follow up period. Conclusions In cases with multi-victims bitten by one dog, except exposure to rabies virus, it is necessary to be alert to the presence of HIV, HBV or HCV infection in sequential victims. Therefore, the risk of the potential spreading of other blood-borne infectious pathogens should be assessed. It is important to initiate PEP as early as possible.

Objective: To understand the prophylaxis of population exposed to rabies, and provide a basis for prevention and control of rabies. Methods: The registration data of 1 019 cases with rabies exposure in Beijing Ditan Hospital Affiliated to Capital Medical University from Mar, 2017 to Feb, 2018 were analyzed using the descriptive epidemiologic method. Results: Among the 1 019 cases of rabies exposure, the sex ratio of men to women was 0.90∶1, with the highest proportion of them were between 26 and 46 years of age old, accounting for 46.5%. Rabies exposure reached its peak (46.9%) between June and September. In addition, 63.3% of the injuries were caused by dogs and 36.7% by cats. Most of the wounds (55.1%) occurred in hands; and the second was lower limbs (26.6%). Most of the cases (60.7%) had grade II wounds; followed by grade III wounds (39.1%); 69.3% of the cases completed immunization with rabies vaccine. In grade III exposure, 73.7% of the patients were immunized with rabies immunoglobulin. Most of the persons of grade III exposure (73.7%) received inoculation with human rabies immunoglobulin (HRIG). Conclusions Measures to control rabies should be focused on the management of dogs and cats and the standardization of rabies post-exposure prophylaxis.

Objective To evaluate the effect of HIV infection and highly active antiretroviral therapy (HAART) on mitochondrial function and mass in peripheral monocytes.Methods There were 14 ART-naive HIV-infected patients,14 NRTI treated HIV-infected patients and 12 healthy controls from Beijing Ditan Hospital.The mitochondrial membrane potential and mitochondrial mass in monocytes were analyzed by flow cytometry.Mitochondrial disturbances related to HIV infection and HAART in monocytes were analyzed.Results In ART-naive patients and NRTI-exposed patients,the levels of mitochondrial membrane potential in monocytes (77.74 ± 14.77,73.94 ± 12.87) were significantly lower than these in healthy controls (89.43 ±4.06) (P =0.032 8,P =0.002 6).The amount of mitochondrial mass in NRTI-exposed patients (3 329.0 ± 836.7) was significantly higher than that in healthy controls (2 075.0 ± 932.2) and that in ART-naive patients (2 592.0 ± 781.5) (P ＜ 0.05).Conclusions The abnormal of mitochondrial membrane potential and mitochondrial mass in monocytes from HIV-infected patients were related to HIV infection and the introduction of HAART.