Biomedical subjects

Jing Lin

Publications and source records attributed to Jing Lin.

At least 19 recordsLinked to original sources

PubMed2026

Spatial proteomics reveals four-stage molecular evolution in cancer immunotherapy-related gastritis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet immune-related adverse events (irAEs) including immunotherapy-related gastritis (IRAEG) pose significant clinical challenges-often necessitating treatment interruption that may compromise antitumor efficacy. IRAEG presents with atypical symptoms, lacks specific biomarkers, and shows histopathological overlap with other forms of gastritis, complicating diagnosis and management. Despite increasing clinical recognition, a systematic understanding of spatial molecular alterations across the full disease course remains limited. Here, we used spatial proteomics to map the molecular landscape of IRAEG during disease progression and to define stage-specific patterns of molecular evolution relevant to cancer immunotherapy management. METHODS: We analyzed tissue samples from seven patients, including four non-immunotherapy-related gastritis controls and three cancer patients who developed IRAEG following ICI therapy for solid tumors, sampled longitudinally across four disease stages: baseline (G1), acute severe inflammation (G2), early recovery (G3), and complete recovery (G4). Using laser capture microdissection coupled with data-independent acquisition mass spectrometry, we profiled 177 spatially resolved gastric tissue regions. Multiplex immunohistochemistry and immunofluorescence characterized features of the immune microenvironment, while Gene Ontology, KEGG pathway analysis, Gene Set Variation Analysis, and xCell inference enabled functional, metabolic, and immune profiling. Key immune and NET-related findings were further validated by multiplex immunofluorescence in an independent, expanded cohort of IRAEG and non-immunotherapy-related gastritis samples. RESULTS: IRAEG was characterized by widespread HLA molecule activation and enhanced antigen processing, resembling the immune phenotype observed in organ transplant rejection. The acute G2 stage exhibited excessive neutrophil extracellular trap formation, profound metabolic suppression, and collapse of immune homeostasis-features that may inform early intervention strategies to preserve ICI treatment continuity. During early recovery (G3), inflammatory injury transitioned toward repair, marked by activation of fatty acid metabolism and PPAR signaling. Notably, even at complete clinical recovery (G4), more than 1,000 proteins remained differentially expressed, reflecting sustained enhancement of metabolic and immune functions and establishing a distinct molecular "memory" state with implications for ICI rechallenge decisions. CONCLUSIONS: These findings define four molecularly distinct stages of IRAEG progression and recovery. The stage-specific signatures identified here serve as candidate biomarkers for diagnosis, disease staging, and therapeutic response assessment, and may guide clinical decisions regarding irAE management, treatment modification, and safe ICI rechallenge to support continued antitumor therapy.

Humans↗

PubMed2025

Differences of clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma and additional primary tumours.

BACKGROUND: The differences in the clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma (MM) and additional primary tumours remain unclear. METHODS: A retrospective analysis was conducted on patients with malignancies in Fujian Cancer Hospital from January 2007 to September 2022, end follow-up in September 2023. Clinical data were gathered, survival analysis was performed, and genetic mutations were detected. RESULTS: There were 58 of 1223 melanoma patients with melanoma and additional primary tumours, an incidence of 4.74%. Acral MM was the most common subtype (26/58), 23 (39.66%) patients had concomitant digestive tumours. Patients who had MM as their first primary tumour (MMFP) had shorter tumour occurrence intervals (9.93 vs. 57.78 months, p = .008) but longer melanoma survival (MM-OS) than the non-MMFP group (100.43 vs. 18.93 months, p = .015). Patients with cancer family histories were more likely to have pathogenic and likely pathogenic (P/LP) mutations (2/5 vs. 4/25). The somatic BRAF gene mutation was frequently observed in MM tissue (8/19, 42.11%). Three patients had whole-genome doubling and microsatellite instability-high (MSI-H). The COSMIC2 signature 3 was significantly higher in the P/LP group. CONCLUSIONS: The frequency of MM and additional primary tumours is about 5% in Chinese populations. Patients with melanoma diagnosed first have longer melanoma survival. Digestive system tumours were the most concomitant; a digestive examination is advisable, especially for those with an expected overall survival (OS) greater than 10 months. Meanwhile, patient's family cancer history should be followed up in detail, along with completion of germline P/LP mutation and somatic mutation testing, all of which may provide valuable support for further treatment.

Adult↗

PubMed2007

Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier.

Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.

Apoptosis↗

PubMed2006

Kinetics of oxidative decolorization and mineralization of Acid Orange 7 by dark and photoassisted Co2+-catalyzed peroxymonosulfate system.

A kinetic model was proposed and used to interpret the experimental data for degradation of Acid Orange 7 (AO7) in aqueous solution induced by Co(2+)/peroxymonosulfate (Co/PMS) reagent in terms of both decolorization and mineralization. The pseudo first-order decolorization rate constants are related to [Co(2+)], [PMS], reciprocal of [H(+)] and [AO7](0). Activation energy of the AO7 decolorization process was determined to be 75.7 kJ mol(-1). UV and visible light can accelerate the decolorization and mineralization process due to different mechanisms. In the combined UV/Co/PMS system, UV light can decompose PMS to generate hydroxyl ((*)OH) and sulfate radicals (SO(4)(*-)), while in the Vis/Co/PMS system, excited AO7 molecules can transfer electrons to PMS or Co(3+) and thus accelerate the decomposition of PMS and catalytic cycle of Co(3+)/Co(2+).

Azo Compounds↗

PubMed2006

Antioxidant activity and hepatoprotective potential of agaro-oligosaccharides in vitro and in vivo.

BACKGROUND: Agaro-oligosaccharides derived from red seaweed polysaccharide have been reported to possess antioxidant activity. In order to assess the live protective effects of agar-oligosaccharides, we did both in vitro and in vivo studies based on own-made agaro-oligosaccharides, and the structural information of this oligosaccharide was also determined. METHOD: Structure of agaro-oligosaccharides prepared with acid hydrolysis on agar was confirmed by matrix-assisted ultraviolet laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and NMR. The antioxidant effect of agaro-oligosaccharides on intracellular reactive oxygen species (ROS) was assessed by 2', 7'-dichlorofluorescin diacetate. Carbon tetrachloride was used to induce liver injury, some index including SOD, GSH-Px, MDA, AST, ALT were examined to determine the hepatoprotective effect of agaro-oligosaccharides. RESULTS: Agaro-oligosaccharides we got were composed of odd polymerizations with molecular weights ranged from 500 to 2500. Results from intracellular test indicated that agaro-oligosaccharides could significantly scavenge the level of oxidants in the hepatocytes, more beneficially, also associated with the improvement of cell viability In vivo studies of the antioxidant effects on tissue peroxidative damage induced by carbon tetrachloride in rat model indicated that agaro-oligosaccharides could elevate the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and decrease the level of malondialdehyde (MDA), glutamate oxaloacetate transaminase (AST), glutamic pyruvic transaminase (ALT) significantly. At 400 mg/kg, MDA level reduced 44 % and 21 % in liver and heart, SOD and GSH-Px increased to highest in liver and serum, while ALT level decreased 22.16 % in serum. CONCLUSION: Overall, the results of the present study indicate that agaro-oligosaccharides can exert their in vitro and in vivo hepatoprotective effect through scavenging oxidative damage induced by ROS.

Agar↗

PubMed2006

A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma.

CD147 plays a critical role in the invasive and metastatic activity of malignant melanoma cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases and vascular endothelial growth factor. We developed a system that blocks CD147 in the human malignant melanoma cell line, A375, using RNA interference. By transfecting melanoma cells with the small interfering RNA (siRNA) that targets human CD147, we were able to establish two stable clones in which CD147 expression was significantly down-regulated. This resulted in the decreased proliferation and invasion of A375 cells in vitro. CD147 siRNA also down-regulated the expression of vascular endothelial growth factor in these cells and reduced the migration of vascular endothelial cells. The reduction in the CD147 level suppressed the size of s.c. tumors and the microvessel density in an A375 s.c. nude mouse xenograft model. In addition, the in vivo metastatic potential of A375 cells transfected with CD147 siRNA was suppressed in a nude mouse model of pulmonary metastasis.

Animals↗

PubMed2006

Template-free preparation of bunches of aligned boehmite nanowires.

A simple method based on a hydrothermal process using alkali salts as mineralizers is proposed for the synthesis of aligned bunches of boehmite (gamma-AlOOH) nanowires without a template's assistance. Most bunches of aligned boehmite nanowires are constructed by two separated shorter bundles with widths of 700 to approximately 800 nm and lengths of about 1 microm. XRD patterns, FTIR spectra, and SEM and TEM images were used to characterize the products. The specific surface area and pore-size distribution of the obtained product as determined by gas-sorption measurements show that the boehmite bundles possess a high BET surface area and porosity properties. The importance of adding Na2B4O7 salts for the formation of bundle morphologies has been discussed.

Journal Article↗

PubMed2006

Synthesis of a technetium-99m labeled tricyclic ganciclovir analog for non-invasive reporter gene expression imaging.

A potential radiopharmaceutical and HSV1-TK substrate, 3-((1,3-dihydroxypropan-2-yloxy)-methyl)-6-(4-(3-((2-mercaptoethyl)(2-(2-mercaptoethyl-amino)-ethyl)amino)propoxy)phenyl)-3H-imidazopurin-9(5H)-one-oxo-technetium(V), was synthesized via a converging approach and its chemical structure was comparatively characterized with a non-radioactive analog. The final radiochemical purity and yield were 97 and 73%, respectively.

Antimetabolites↗

PubMed2006

Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B.

S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins. A consensus sequence for S100B target proteins was published as (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (V.V. Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ, J. Biol. Chem. 270 (1995) 14651-14658). Several additional S100B targets are known including p53, a nuclear Dbf2 related (NDR) kinase, the RAGE receptor, neuromodulin, protein kinase C, and others. Examining the binding sites of such targets and new protein sequence searches provided additional potential target proteins for S100B including Hdm2 and Hdm4, which were both found to bind S100B in a calcium-dependent manner. The interaction between S100B and the Hdm2 and/or the Hdm4 proteins may be important physiologically in light of evidence that like Hdm2, S100B also contributes to lowering protein levels of the tumor suppressor protein, p53. For the S100B-p53 interaction, it was found that phosphorylation of specific serine and/or threonine residues reduces the affinity of the S100B-p53 interaction by as much as an order of magnitude, and is important for protecting p53 from S100B-dependent down-regulation, a scenario that is similar to what is found for the Hdm2-p53 complex.

Amino Acid Sequence↗

PubMed2006

Self-assembly of flowerlike AlOOH boehmite 3D nanoarchitectures.

In this work, a hydrothermal route using an ethanol-water solution to progressively synthesize a sequence of flowerlike three-dimensional gamma-AlOOH boehmite nanostructures without employing templates or matrixes for self-assembly is presented. The flowerlike boehmite nanoarchitectures exhibit three hierarchies of self-organization, i.e., single-crystalline nanorods, nanostrips, and bundles, which are characterized by scanning and transmission electron microscopy. The sequence of products obtained after different processing times indicates a self-assembly mechanism. The hydrogen bonding on the surface of nanorods or nanostrips possibly plays a key role, as identified by FTIR spectra of the products after they had been heated to 1000 degrees C. The specific surface area and pore-size distribution of the obtained product as determined by gas-sorption measurements show that the boehmite nanoarchitectures exhibit high BET surface area and porosity properties.

Journal Article↗

PubMed2006

The potential allergenicity of two 2S albumins from soybean (Glycine max): a protein microarray approach.

BACKGROUND: The 2S albumins are a group of storage proteins that occur widely in seeds of dicotyledonous plants. The widespread distribution and stability to digestion of allergenic 2S albumins raise the question of why some members of this family present in important food sources, such as soybean, are not regarded as major allergens. METHODS: The pepsinolytic stability of two 2S albumins from soybean seed was determined using simulated gastric fluid. Using a new protein microarray system, IgE binding to these soybean 2S albumins was studied with the sera from 23 European individuals allergic to soybean. In order to validate the microarray result, two of the sera were selected and further tested using the micro-ELISA and UniCAP system. RESULTS: Both albumins exhibited high stability to digestion similar to other allergenic members of the 2S albumin, trypsin/amylase inhibitor and lipid transfer protein superfamily. None of the patients was found to have IgE specific to soybean 2S albumins by the microarray system, and this result was in agreement with the results from the micro-ELISA and UniCAP system. CONCLUSIONS: The results from microarray, micro-ELISA and UniCAP system suggested that the 2S albumins from soybean are not major allergens within the patient population analyzed.

Albumins↗

PubMed2006

Fascaplysin, a selective CDK4 inhibitor, exhibit anti-angiogenic activity in vitro and in vivo.

PURPOSE: This study was to evaluate the correlation of two important strategies, namely, cell cycle proliferation arrest and anti-angiogenesis. We chose fascaplysin, a marine natural product with selective CDK4 selective inhibition activity, to study its potential anti-angiogenesis effects in vivo and in vitro. METHODS: Chorioallantoic membrane (CAM) assay was initially used as an in vivo approach to evaluate anti-angiogenic activity of fascaplysin. In addition, human umbilical vein endothelial cell (HUVEC) line was used to further confirm the anti-angiogenic activity of fascaplysin in vitro. To explore the mechanism of anti-angiogenesis, we examined the effect of fascaplysin on vascular endothelial growth factor (VEGF) expression and secretion by hepatocarcinoma cells BeL-7402. RESULTS: The results of CAM assay suggested fascaplysin inhibited capillary plexus formation in a dose-dependent manner and suppressed VEGF in cross section. Moreover, the in vitro assay also confirmed that fascaplysin provided selective inhibition of endothelial cells proliferation towards tumor cells in low concentration. The immunocytochemical staining and ELISA verified fascaplysin could inhibit VEGF expression and secretion by BeL-7402. CONCLUSIONS: These findings strongly suggest that fascaplysin is a natural angiogenesis inhibitor.

Angiogenesis Inhibitors↗

PubMed2006

[The influence of CD14 genomic polymorphism on CD14 gene expression as well as protein release and its clinical significance in patients with extensive burns].

OBJECTIVE: To investigate the influence of a lipopolysaccharide receptor CD14-159C/T genomic polymorphism on CD14 gene expression as well as protein release, and the relation of sepsis susceptibility and prognosis in patients with extensive burns. METHODS: The study group consisted of 26 patients with burns covering more than 30% of the total body surface area. The CD14 gene polymorphism was determined by polymerase chain reaction (PCR) and subsequent HaeIII restriction enzyme digestion of the PCR products. Meanwhile, the association of CD14, TNF-alpha mRNA expression in leukocytes and soluble CD14 (sCD14) levels in serum with CD14-159 polymorphism as well as prognosis after burns was also studied. RESULTS: The T allele frequencies in sepsis patients and non-survivors were higher than those in non-septic patients and survivors. The levels of CD14 mRNA, TNF-alpha mRNA expression and serum sCD14 were significantly different among patient groups with TT, TC, and CC genotypes. The above differences were also existed between survivors and non-survivors. CD14 mRNA expression was higher in heterozygotes (TT and TC) than in C homozygous patients (P < 0.05 or P < 0.01), and sCD14 level was higher in heterozygotes (TC) than C homozygous patients on day 7 postburn (P < 0.05). During the 28-day observation period, mean TNF-alpha mRNA expression was higher in patients homozygous for T allele than C homozygotes (P < 0.05). In addition, higher CD14 mRNA values were found in non-survivors compared to those in survivors on days 7 and 28 postburn (P < 0.05). CONCLUSIONS: CD14C-159T polymorphism might markedly influence CD14 mRNA expression and sCD14 levels, and it seems to be associated with sepsis susceptibility and prognosis in patients with extensive burns. The T allele could be a genetic risk marker of adverse prognosis.

Adult↗

PubMed2006

Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections.

OBJECTIVE: The histopathologic abnormality underlying ascending aortic aneurysm and dissection is medial degeneration, a lesion that is described as the noninflammatory loss of smooth muscle cells and elastic fibers. This study sought to determine whether inflammatory cells are present in medial degeneration and assess any possible contribution of these cells to apoptosis of smooth muscle cells. METHODS: Aortic specimens were obtained from patients undergoing prophylactic surgical repair of an ascending aortic aneurysm (n = 9) and type A dissection (n = 7), along with control patients dying of causes unrelated to aortic disease (n = 5). Immunohistochemical staining was performed to evaluate the presence of lymphocytes and macrophages, and markers of apoptosis were assessed in the aortas of patients with ascending aortic aneurysm and dissection. RESULTS: Immunohistochemical study indicated significantly more CD3+ cells in the aortas of patients with aneurysms or dissections than in control aortas (P = .020 and P = .0022, respectively). In addition, aortas of patients with aneurysms or dissections had more CD68+ cells (P = .01 and P = .005, respectively). CD3+ cells were localized in the media and surrounding the vasa vasorum in the adventitia. Cells yielding a positive result on in situ terminal transferase-mediated deoxyuridine triphosphate nick end-labeling were found in increased numbers in the aortas of patients with aneurysms or dissections relative to control aortas (P = .005 and P = .002, respectively). Furthermore, Fas and FasL were increased in the aortic samples from patients with aneurysms and dissections relative to control aortas. CONCLUSION: The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aortas with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix associated with thoracic aortic aneurysms and dissections.

Aortic Dissection↗

PubMed2006

A comparison of standard immunogenicity assays for monitoring HIV type 1 gag-specific T cell responses in Ad5 HIV Type 1 gag vaccinated human subjects.

Currently, there are numerous candidate HIV vaccines aimed at inducing T-cell mediated immune responses against HIV. To assess the immunogenicity of such vaccines, a reliable T cell assay must be utilized and typically one of the following assays is chosen for this purpose: bulk culture CTL, MHC I tetramer staining, IFN-gamma ELISPOT, or IFN-gamma intracellular cytokine staining. In this paper we report a comparison of the T cell responses detected by each assay in a large cohort of healthy normal volunteers vaccinated with adenovirus serotype 5 expressing HIV gag. Using stringently validated formats of each of these assays and pools of overlapping HIV gag peptides, we demonstrate that there is a high degree of correlation between all four of the common T cell assays, but inherent differences in the sensitivity of each assay to detect responders. In this study, the ELISPOT assay is shown to have the greatest sensitivity in detecting vaccine responses, while the ICS assay, although less sensitive, has the advantage of providing additional information on the phenotype of the responding cells.

AIDS Vaccines↗

PubMed2006

Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239.

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4(+) memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

Animals↗

PubMed2006

[Long-term follow-up results of synovectomy for rheumatoid knee].

OBJECTIVE: To continuously observe the long-term effects of synovectomy for improving joint damage and quality-of-life in patients with the rheumatoid knee. METHODS: Twenty-one consecutive patients with rheumatoid arthritis (RA) involving 24 knees underwent open synovectomy from November 1988 to January 1997 between November 1988 and January 1997. The changes in radiographic damage were assessed with Larsen score on plain films before and 6 months after surgery with subsequent annual assessment for 8 years, and the functional recovery of the patients was also evaluated with Health Assessment Questionnaire (HAQ) at the same time. RESULTS: The radiographic joint damage and juxta-articular osteoporosis or bone erosion was ameliorated after surgery in all the patients. Larsen score began to decrease 6 months after the operation, and the best effects were achieved at one year and maintained for at least 5 years after the operation, but then followed by recurrence of joint lesions. HAQ scores were improved after the surgery with the best effects observed 6 months after the operation lasting for over 2 years. HAQ score gradually decreased 4 years after the operation till reaching the preoperative scores. CONCLUSION: Synovectomy in the patients with rheumatoid knee not only reverses progressive joint damage, but also improves juxta-articular bone erosions and the patients' quality of life. However, radiographic joint damage and functional deterioration may recur due to hyperplasia of the inflammatory synovium in the long term after operation, suggesting that the inflammatory synovium participates in local joint damage with bone erosions and systemic pathologic process of RA.

Adult↗

PubMed2005

Effects of hepatitis B virus on p53 expression in hepatoma cell line SMMU-7721.

AIM: To investigate the contribution of HBV in the development of hepatocarcinoma by examining the effects of HBV on p53 function in SMMU-7721 cell line. METHODS: Plasmid pCMVp53 was transfected or cotransfected with pCMVHBVa (wild-type HBV) or PCMVHBVb (mutation type HBV) into the hepatoma cell line SMMU-7721 by lipofectamine. Apoptosis cells were labeled with annexin V-FITC and confirmed by flow cytometry. Reporter plasmid PG13-CAT or p21-luc was cotransfected, respectively, into each group to determine the transactivation activity of p53 and its effect on p21 promoter. Western blot was performed to observe p53 expression in hepatoma cell line of each group. RESULTS: The group transfected with pCMVp53 alone exhibited higher luciferase activity and higher apoptosis rate, otherwise, the p53 expression and reporter activity of PG13-CAT or P21-luc as well as cell apoptosis rate were obviously higher in the group cotransfected of pCMVp53 with pCMVHBVa, but not in the other cotransfected group. CONCLUSION: Transient transfection of HBV into the SMMU-7721 cell line can enhance p53 expression and its effects on development of hepatocarcinoma.

Apoptosis↗