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Biomedical subjects

Hong Zhu

Publications and source records attributed to Hong Zhu.

At least 19 recordsLinked to original sources
PubMed2026

The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.

BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.

Humans↗
PubMed2026

HLA-DQB1*06:02 and a critical amino acid variant in protection against occult hepatitis B virus infection.

The human leukocyte antigen (HLA) system plays a critical role in determining the outcomes of hepatitis B virus (HBV) infection, yet the genetic mechanisms underlying occult HBV infection (OBI), a form marked by detectable HBV DNA in the absence of hepatitis B surface antigen, remain poorly defined. Here, we performed high-resolution HLA genotyping and amino acid-based association analysis in a Chinese population comprising 239 OBI cases and 545 healthy controls. We identified the HLA class II allele DQB1*06:02 as a protective signal against OBI, with conditional analysis confirming its independent effect. This allele is carried on the conserved haplotype DRB1*15:01~DQA1*02:01~DQB1*06:02, which was significantly underrepresented in OBI cases. Conversely, the DRB1*09:01~DQA1*03:02~DQB1*03:03 haplotype was associated with increased OBI risk. Analysis of the HLA-DQB1 amino acid residues revealed that position 119, located in an α-helix of the peptide-binding groove, drives a substantial portion of the observed association. The phenylalanine variant at this site remained strongly protective after multiple-testing correction and is encoded by DQB1*06:02. Our study thus delineates both allele and amino acid level HLA determinants of OBI susceptibility, highlighting a key structural residue that may influence antigen presentation and immune clearance of HBV. These findings provide a refined genetic framework for understanding host and virus interactions in occult HBV persistence.

Humans↗
PubMed2007

Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors alpha and beta.

Neurogenesis persists throughout life under normal and degenerative conditions. The adult subventricular zone (SVZ) generates neural stem cells capable of differentiating to neuroblasts and migrating to the site of injury in response to brain insults. In the present study, we investigated whether estradiol increases neurogenesis in the SVZ in an animal model of stroke to potentially promote the ability of the brain to undergo repair. Ovariectomized C57BL/6J mice were implanted with capsules containing either vehicle or 17beta-estradiol, and 1 week later they underwent experimental ischemia. We utilized double-label immunocytochemistry to identify the phenotype of newborn cells (5-bromo-2'-deoxyuridine-labeled) with various cellular markers; doublecortin and PSA-NCAM as the early neuronal marker, NeuN to identify mature neurons, and glial fibrillary acidic protein to identify astrocytes. We report that low physiological levels of estradiol treatment, which exert no effect in the uninjured state, significantly increase the number of newborn neurons in the SVZ following stroke injury. This effect of estradiol is limited to the dorsal region of the SVZ and is absent from the ventral SVZ. The proliferative actions of estradiol are confined to neuronal precursors and do not influence gliosis. Furthermore, we show that both estrogen receptors alpha and beta play pivotal functional roles, insofar as knocking out either of these receptors blocks the ability of estradiol to increase neurogenesis. These findings clearly demonstrate that estradiol stimulates neurogenesis in the adult SVZ, thus potentially facilitating the brain to remodel and repair after injury.

Animals↗
PubMed2007

Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury.

Substantial evidence suggests a crucial role for glutathione (GSH) and GSH-linked enzymes in protecting against oxidative vascular disorders. However, studies on the chemical inducibility of these antioxidant defenses and their protective effects on oxidant injury in normal human vascular cells are currently lacking. Accordingly, this study was undertaken to investigate the inducibility of GSH, glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST) by the chemoprotective agent, 3H-1,2-dithiole-3-thione (D3T) in cultured normal human aortic smooth muscle cells (HASMCs). HASMCs expressed measurable levels/activities of GSH, GR, GPx, and GST. Incubation of HASMCs with low micromolar concentrations of D3T resulted in a marked elevation in total cellular GSH content and GR activity. The protein and mRNA expression of gamma-glutamylcysteine ligase (GCL) and GR were also upregulated by D3T. In addition, D3T caused significant increases in mitochondrial GSH content and GR activity. In contrast, neither cellular GPx nor GST activity was altered after D3T treatment. Pretreatment of HASMCs with D3T afforded remarkable protection against reactive oxygen and nitrogen species (ROS/RNS)-mediated cell injury. Depletion of cellular GSH by pretreatment with buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis led to marked potentiation of the ROS/RNS-induced cell injury. Moreover, co-treatment of HASMCs with BSO was found to completely abolish the D3T-mediated GSH elevation, and remarkably reverse D3T cytoprotection against the ROS/RNS-elicited injury. Taken together, this study demonstrates that both GSH/GCL and GR in normal HASMCs are inducible by D3T, and that upregulation of GSH biosynthesis appears to be the predominant mechanism underlying D3T-mediated cytoprotection against ROS/RNS-elicited injury to human vascular smooth muscle cells.

Antineoplastic Agents↗
PubMed2007

Molecular genetic analysis of Wanggu remains, Inner Mongolia, China.

The Wanggu tribe, which contributed significantly to the foundation of the Yuan Dynasty, was one of the groups living on the Mongolian steppes during the Jin-Yuan period (AD 1127-1368) of Chinese history. However, there has been both archaeological and historical dispute regarding the origin of the ancient tribe. Recently, we discovered human remains of the Wanggu tribe in the Chengbozi cemetery in the Siziwang Banner of Inner Mongolia, China. To investigate the genetic structure of the Wanggu tribe and to trace the origins of the tribe at a molecular level, we analyzed the control-region sequences and coding regions of mitochondrial DNA (mtDNA) from the remains by direct sequencing and restriction-fragment length polymorphism analysis. In combination with mtDNA data of 15 extant Eurasian populations, we performed phylogenetic analysis and multidimensional scaling analysis. Our results show that the genetic structure of the Wanggu tribe in the Jin-Yuan period is a complex matriline, containing admixture from both Asian and European populations. In addition, we reveal that on the basis of mtDNA data, the ancient tribe may share a recent common ancestor with the Turkic-speaking Uzbeks and Uighurs.

Adolescent↗
PubMed2006

Small interfering RNAs targeting mutant K-ras inhibit human pancreatic carcinoma cells growth in vitro and in vivo.

AIM: To investigate the effect of small interfering RNAs targeting mutant K-ras on the growth of pancreatic carcinoma cell lines in vitro and in vivo. MATERIALS AND METHODS: We cloned targeting sequence spanning codon 12 of mutant K-ras into the pSilencer-hygro plasmid, yielding two recombinant vectors with one base different. Both human pancreatic carcinoma cell lines were transfected by these two recombinant vectors. The transfected PC-7 cells were injected subcutaneously into nude mice to observe its tumorigenicity. RT-PCR and Western blot analysis were carried out to test the expression of K-ras in all of the transfected cell lines. Growth curves assay were performed to test the abilities of cells proliferation. Anti-K-ras therapy of PC-7 and Panc-1 in subcutaneous mice models were performed by intratumor injection of polyethylenimine/siRNAs complex. RESULTS: The expressions of K-ras in PC-7 cells and Panc-1 cells were significantly inhibited by corresponding small interfering RNAs. The expression of K-ras was particularly inactivated by siRNA without any base mismatch to its homologous mRNA, while this oncogene with central base mismatch could not be inhibited as effectively as that of the former. The growth of PC-7 cells and Panc-1 cells transfected by corresponding mutant K-ras targeted siRNAs were significantly suppressed when compared with controls (p<0.05). The transfected PC-7 cells lost tumorigenic ability. Four weeks treatment of Xenograft of pancreatic carcinoma (PC-7 and Panc-1) in nude mice with Polyethylenimine-encapsulated mutant K-ras targeted siRNAs (20 microg/mouse twice weekly) were effective in reducing tumor growth, when compared with controls (p<0.05). CONCLUSION: The central base may play a key role in the process of RNA interference. The mutant point and its vicinity of 19 nucleotides in K-ras may be the effective targeting sequence for RNA interference. Targeting mutant-k-ras therapy of pancreatic carcinoma may be a clinically applicable therapeutic modality.

Cell Division↗
PubMed2006

Isolated and characterization of a cDNA encoding ethylene-responsive element binding protein (EREBP)/AP2-type protein, RCBF2, in Oryza sativa L.

A transcription factor RCBF2 which interacts with C-repeat/DRE was isolated from Oryza sativa L. by a yeast one-hybrid method. Analysis of the deduced RCBF2 amino acid sequence revealed that RCBF2 contained a conserved ethylene-responsive element binding protein (EREBP)/AP2 domain of 59 amino acids and a potential nuclear localization sequence. RCBF2 showed a high level of homology with other CBF family members only in AP2 domain. Phylogenetic analysis showed that RCBF2 might be different from other eight DRE-binding proteins on evolutionary relationship. The semi-quantitative RT-PCR (s-Q RT-PCR) analysis indicated the expression of RCBF2 gene was induced by cold, dehydration and high-salinity, but not by abscisic acid, and the transcription of RCBF2 gene accumulated primarily in rice immature seeds, growing point and shoots.

Base Sequence↗
PubMed2006

Elastin-like polypeptide fusions enhance the accumulation of recombinant proteins in tobacco leaves.

The production of recombinant proteins in plants is an active area of research and many different high-value proteins have now been produced in plants. Tobacco leaves have many advantages for recombinant protein production particularly since they allow field production without seeds, flowers or pollen and therefore provide for contained production. Despite these biosafety advantages recombinant protein accumulation in leaves still needs to be improved. Elastin-like polypeptides are repeats of the amino acids "VPGXG" that undergo a temperature dependant phase transition and have utility in the purification of recombinant proteins but can also enhance the accumulation of recombinant proteins they are fused to. We have used a 11.3 kDa elastin-like polypeptide as a fusion partner for three different target proteins, human interleukin-10, murine interleukin-4 and the native major ampullate spidroin protein 2 gene from the spider Nephila clavipes. In both transient analyses and stable transformants the concentrations of the fusion proteins were at least an order of magnitude higher for all of the fusion proteins when compared to the target protein alone. Therefore, fusions with a small ELP tag can be used to significantly enhance the accumulation of a range of different recombinant proteins in plant leaves.

Elastin↗
PubMed2006

Complement-dependent P-selectin expression and injury following ischemic stroke.

The mechanisms that contribute to inflammatory damage following ischemic stroke are poorly characterized, but studies indicate a role for both complement and P-selectin. In this study, we show that compared with wild-type mice, C3-deficient mice showed significant improvement in survival, neurological deficit, and infarct size at 24 h after middle cerebral artery occlusion and reperfusion. Furthermore, P-selectin protein expression was undetectable in the cerebral microvasculature of C3-deficient mice following reperfusion, and there was reduced neutrophil influx, reduced microthrombus formation, and increased blood flow postreperfusion in C3-deficient mice. We further investigated the use of a novel complement inhibitory protein in a therapeutic paradigm. Complement receptor 2 (CR2)-Crry inhibits complement activation at the C3 stage and targets to sites of complement activation. Treatment of normal mice with CR2-Crry at 30 min postreperfusion resulted in a similar level of protection to that seen in C3-deficient mice in all of the above-measured parameters. The data demonstrate an important role for complement in cerebrovascular thrombosis, inflammation, and injury following ischemic stroke. P-selectin expression in the cerebrovasculature, which is also implicated in cerebral ischemia and reperfusion injury, was shown to be distal to and dependent on complement activation. Data also show that a CR2-targeted approach of complement inhibition provides appropriate bioavailability in cerebral injury to enable complement inhibition at a dose that does not significantly affect systemic levels of serum complement activity, a potential benefit for stroke patients where immunosuppression would be undesirable due to significantly increased susceptibility to lung infection.

Animals↗
PubMed2006

Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.

We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.

Animals↗
PubMed2006

Pathology of the thyroid in severe acute respiratory syndrome.

The severe acute respiratory syndrome (SARS) epidemic started in November 2002 and spread worldwide. The pathological changes in several human organs of patients with SARS have been extensively described. However, to date, little has been reported about the effects of this infection on the thyroid gland. Femoral head necrosis and low serum triiodothyronine and thyroxine levels, commonly found in patients with SARS, raise the possibility of thyroid dysfunction. We have undertaken this study to evaluate for any potential injury to the thyroid gland caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay was performed to identify apoptotic cells. The follicular epithelium was found to be damaged with large numbers of cells exfoliated into the follicle. The terminal deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay demonstrated many cells undergoing apoptosis. Follicular architecture was altered and showed distortion, dilatation, and collapse. No distinct calcitonin-positive cells were detectable in the SARS thyroids. In conclusion, both parafollicular and follicular cells were injured. This may provide an explanation both for low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients with SARS. Apoptosis may play a role in the pathogenesis of SARS associated coronavirus infection in the thyroid gland.

Adult↗
PubMed2006

Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals.

Tetrathiatriarylmethyl (TAM) radicals are commonly used as oximetry probes for electron paramagnetic resonance imaging applications. In this study, the electronic properties and the thermodynamic preferences for O2 addition to various TAM-type triarylmethyl (trityl) radicals were theoretically investigated. The radicals' stability in the presence of O2 and biological milieu was also experimentally assessed using EPR spectroscopy. Results show that H substitution on the aromatic ring affects the trityl radical's stability (tricarboxylate salt 1-CO2Na > triester 1-CO2Et > diester 2-CO2Et > monoester 3-CO2Et) and may lead to substitution reactions in cellular systems. We propose that this degradation process involves an arylperoxyl radical that can further decompose to alcohol or quinone products. This study demonstrates how computational chemistry can be used as a tool to rationalize radical stability in the redox environment of biological systems and aid in the future design of more biostable trityl radicals.

Electron Spin Resonance Spectroscopy↗
PubMed2006

SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor.

1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2-caroxylate (SH-7), a new naphthoquinone compound, derived from shikonin, exhibited obvious inhibitory actions on topoisomerase II (Topo II) and topoisomerase I (Topo I), which were stronger than its mother compound shikonin. Notably, the SH-7's inhibitory potency on Topo II was much stronger than that on Topo I. In addition, SH-7 significantly stabilized Topo II-DNA cleavable complex and elevated the expression of phosphorylated-H2AX. The in vitro cell-based investigation demonstrated that SH-7 displayed wide cytotoxicity in diversified cancer cell lines with the mean IC(50) value of 7.75 microM. One important finding is SH-7 displayed significant cytotoxicity in the 3 MDR cell lines, with an average IC(50) value nearly equivalent to that of the corresponding parental cell lines. The average resistance factor (RF) of SH-7 was 1.74, which was much lower than those of reference drugs VP-16 (RF 145.92), ADR (RF 105.97) and VCR (RF 197.39). Further studies illustrated that SH-7 had the marked apoptosis-inducing function on leukemia HL-60 cells, which was validated to be of mitochondria-dependence. The in vivo experiments showed that SH-7 had inhibitory effects on S-180 sarcoma implanted to mice, SMMC-7721, BEL-7402 human hepatocellular carcinoma and PC-3 human prostate cancer implanted to nude mice. Taken together, these results suggest that SH-7 induces DSBs as a Topo II inhibitor, which was crucial to activate the apoptotic process, and subsequently accounts for its both in vitro and in vivo antitumor activities. The well-defined Topo II inhibitory activity, antitumor effects particularly with its obvious anti-MDR action, better solubility and less toxicity make SH-7 as a potential antitumor drug candidate for further research and development.

Animals↗
PubMed2006

Lateralization of olfaction in the honeybee Apis mellifera.

Lateralization of function is a well-known phenomenon in humans. The two hemispheres of the human brain are functionally specialized such that certain cognitive skills, such as language or musical ability, conspecific recognition, and even emotional responses, are mediated by one hemisphere more than the other [1, 2]. Studies over the past 30 years suggest that lateralization occurs in other vertebrate species as well [3-11]. In general, lateralization is observed in different sensory modalities in humans as well as vertebrates, and there are interesting parallels (reviewed in [12]). However, little is known about functional asymmetry in invertebrates [13, 14] and there is only one investigation in insects [15]. Here we show, for the first time, that the honeybee Apis mellifera displays a clear laterality in responding to learned odors. By training honeybees on two different versions of the well-known proboscis extension reflex (PER) paradigm [16, 17], we demonstrate that bees respond to odors better when they are trained through their right antenna. To our knowledge, this is the first demonstration of asymmetrical learning performance in an insect.

Animals↗
PubMed2006

Enhanced neuropeptide Y immunoreactivity and vasoconstriction in mesenteric small arteries from the early non-obese diabetic mouse.

The present study investigated whether sympathetic neurotransmission is altered at an early stage of diabetes in mesenteric small arteries isolated from female non-obese diabetic (NOD) and control animals without diabetes from the same mouse strain. The NOD diabetic mice had increased plasma glucose and hypertension. Confocal microscopy showed distribution of nerve terminals was similar, but immunoreaction intensity for neuropeptide Y (NPY) and tyrosine hydroxylase was higher in small arteries from NOD diabetic compared with NOD control mice. In the presence of prazosin and activated with vasopressin, electrical field stimulation evoked contractions which were more pronounced in mesenteric arteries from NOD diabetic versus NOD control mice and inhibited by the NPY Y(1) receptor antagonist, BIBP 3226. NPY concentration-response curves were leftward shifted in arteries from NOD diabetic versus NOD control both in arteries with and without endothelium, but not in the presence of the BIBP 3226. The present findings suggest that enhanced NPY content and vasoconstriction to NPY by activation of NPY Y(1) receptors in arteries from diabetic mice may contribute to the enhanced sympathetic nerve activity and vascular resistance in female non-obese early diabetic animals.

Animals↗
PubMed2006

Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress.

Understanding the molecular pathway(s) controlling the expression of stromal cellular antioxidants and phase 2 enzymes is of importance for developing strategies to protect against bone marrow toxicity induced by oxidants and electrophiles. Accordingly, this study was undertaken to determine the role of the nuclear factor E2-related factor 2 (Nrf2) in regulation of both constitutive and chemoprotectant-inducible expression of antioxidants and phase 2 enzymes in mouse bone marrow stromal cells. The constitutive expression of a series of antioxidants and phase 2 enzymes was significantly lower in stromal cells derived from Nrf2 knockout (Nrf2(-/-)) mice than those from wild-type littermates (Nrf2(+/+)). Incubation of Nrf2(+/+) stromal cells with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of various antioxidants and phase 2 enzymes. The inducibility of the above cellular defenses by D3T was abolished in Nrf2(-/-) cells. As compared to wild-type cells, Nrf2(-/-) cells were much more susceptible to cytotoxicity induced by reactive oxygen or nitrogen species, 4-hydroxy-2-nonenal, 1,4-hydroquinone, or 1,4-benzoquinone. Upregulation of the antioxidants and phase 2 enzymes by D3T in Nrf2(+/+) stromal cells resulted in increased resistance to the above oxidant- and electrophile-induced cytotoxicity, whereas D3T treatment of Nrf2(-/-) cells only provided a marginal cytoprotection. Taken together, this study demonstrates that Nrf2 is crucial in controlling the expression of bone marrow stromal antioxidants and phase 2 enzymes as well as the susceptibility of these cells to oxidative and electrophilic stress.

Animals↗
PubMed2006

Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death.

Estradiol enhances plasticity and survival of the injured brain. Our previous work demonstrates that physiological levels of estradiol protect against cerebral ischemia in the young and aging brain through actions involving estrogen receptors (ERs) and alterations in gene expression. The major goal of this study was to establish mechanisms of neuroprotective actions induced by low levels of estradiol. We first examined effects of estradiol on the time-dependent evolution of ischemic brain injury. Because estradiol is known to influence apoptosis, we hypothesized that it acts to decrease the delayed phase of cell death observed after middle cerebral artery occlusion (MCAO). Furthermore, because ERs are pivotal to neuroprotection, we examined the temporal expression profiles of both ER subtypes, ERalpha and ERbeta, after MCAO and delineated potential roles for each receptor in estradiol-mediated neuroprotection. We quantified cell death in brains at various times after MCAO and analyzed ER expression by RT-PCR, in situ hybridization, and immunohistochemistry. We found that during the first 24 h, the mechanisms of estradiol-induced neuroprotection after MCAO are limited to attenuation of delayed cell death and do not influence immediate cell death. Furthermore, we discovered that ERs exhibit distinctly divergent profiles of expression over the evolution of injury, with ERalpha induction occurring early and ERbeta modulation occurring later. Finally, we provide evidence for a new and functional role for ERalpha in estradiol-mediated protection of the injured brain. These findings indicate that physiological levels of estradiol protect against delayed cell death after stroke-like injury through mechanisms requiring ERalpha.

Animals↗