Xiaole Chen's research while affiliated with Julphar School of Pharmacy and other places

Publications (35)

Preprint
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MYOC mutations are the leading genetic causes of primary open-angle glaucoma (POAG). We previously identified a recurrent Gly367Arg mutant myocilin (MYOC/p.G367R) associated with juvenile open-angle glaucoma (JOAG) in a large Chinese family, but the pathogenic mechanism remains unclear. The MYOC/p.G367R carrier presented a high intraocular pressure...
Article
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Long non-coding RNA (lncRNA) is involved in the regulation of rheumatoid arthritis (RA) and many other diseases. In this study, a new lncRNA, NR-133666, was identified to be highly expressed in the adjuvant-induced arthritis rat model using the Agilent lncRNA microarray assay. qRT-PCR verified that NR-133666 was upregulated in fibroblast-like synov...
Article
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Sepsis caused by a dysregulated host response to infection is a life-threatening disease that can lead to organ dysfunction. Due to its unclear and complex mechanism, effective medicine for the treatment of sepsis is urgently required. The extensive release of cytokines and other mediators like TNF-α and interleukin-6 (IL-6) play critical roles in...
Article
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The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractiv...
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Lapatinib is an FDA-approved EGFR and HER2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer patients. However, its therapeutic efficacy is limited by primary or acquired resistance. In the present study, we established breast cancers cells with acquired lapatinib resistance and investigated the antitumor activity of the se...
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Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a d...
Preprint
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Context: It is urgent to develop drugs with independent intellectual property rights and more reasonable price, safe and effective treatment of RA. Objective: To study the inhibitory effect of curcumin derivative FM0807 on the proliferation of RA-FLS cells and its possible mechanism. Materials&Methods: Rheumatiod arthritis fibroblast-like synoviocy...
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Retinal degeneration diseases (RDDs) are common and devastating eye diseases characterized by the degeneration of photoreceptors, which are highly associated with oxidative stress. Previous studies reported that mitochondrial dysfunction is associated with various neurodegenerative diseases. However, the role of mitochondrial proteostasis mainly re...
Preprint
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A novel anti-TNF-α/IL-6R triple-specific fusion protein, by linking 3 single domain chains, was designed and constructed in our lab. The high purity fusion proteins were obtained by our developed prokaryotic expression system process with high binding affinity with TNF-α (94.75 pM), Human Serum Albumin (1.83 nM) and IL-6R (2.29 nM). In this study,...
Preprint
Full-text available
The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractiv...
Article
Purpose: To investigate the protective effects of nicotinamide riboside (NR) on oxidative damage in hydrogen peroxide (H2O2)-exposed human lens epithelial cell lines (SRA01/04) and the possible mechanisms underlying its protective effects. Materials and methods: SRA01/04 cells were divided into three groups: the control (CON) group, model (H2O2) gr...
Article
Full-text available
The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signaling that cause collateral damage to protective signaling cascades carrying the potential for unwanted side effects. The variable domains of heavy-chain only antibodies (HCAbs) discovered in Camelidae are stable and display to be fully fun...
Article
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Objective To determine the effect of ropivacaine on peripheral neuropathy in diabetic rats and its possible mechanism. Methods Forty-eight Sprague–Dawley rats were randomly divided into six groups: nondiabetic control group, nondiabetic group A (0.25% ropivacaine), nondiabetic group B (0.75% ropivacaine), diabetic control group (diabetic peripheral...
Article
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Background: Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]...
Article
Purpose: To identify mutations in crystallin genes in Chinese families with congenital cataracts. Methods: Forty-two unrelated families with non-syndromic congenital cataracts were enrolled in this study. The coding exons and adjacent intronic regions of crystallin genes, including CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRY...
Article
Microwave-assisted copper-catalyzed cascade reactions between 2-halobenzoic acids and amidines to synthesize quinazolinone derivatives in water are reported. A variety of target products were obtained in good to excellent yields up to 94%. Its application was performed by the synthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-6-methoxypteridine, which d...
Article
Full-text available
Purpose: Sepsis is a systemic inflammatory response caused by infection. Curcumin is known to have antioxidant and anti-inflammatory activities. FM0807, a curcumin derivative, was investigated in this study to determine its effect on cytokines and the possible molecular mechanism. Main methods: The experiments were carried out in lipopolysacchar...
Article
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Background Congenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts. Met...
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A proteomic and transcriptomic comparative analysis of the venoms of three Atheris species (A. squamigera, A. nitschei and A. chlorechis) was carried out by size exclusion liquid chromatography, gel electrophoresis, mass spectrometry, and mRNA sequencing. The improved proteomic profiling utilised in this work was combined with transcript studies, a...
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Heat shock protein 90 (Hsp90) contains amino (N)-terminal domain, carboxyl(C)-terminal domain, and middle domains, which activate Hsp90 chaperone function cooperatively in tumor cells. One terminal occupancy might influence another terminal binding with inhibitor. The Bcr-Abl kinase is one of the Hsp90 clients implicated in the pathogenesis of chro...
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The chemical compounds synthesised and secreted from the dermal glands of amphibian have diverse bioactivities that play key roles in the hosts’ innate immune system and in causing diverse pharmacological effects in predators that may ingest the defensive skin secretions. As new biotechnological methods have developed, increasing numbers of novel p...
Article
Amphibian skin secretions contain biologically-active compounds, such as anti-microbial peptides and trypsin inhibitors, which are used by biomedical researchers as a source of potential novel drug leads or pharmacological agents. Here, we report the application of a recently developed technique within our laboratory to "shotgun" clone the cDNAs en...
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Secretory phospholipase A₂ (sPLA₂) is known as a major component of snake venoms and displays higher-order catalytic hydrolysis functions as well as a wide range of pathological effects. Atheris is not a notoriously dangerous genus of snakes although there are some reports of fatal cases after envenomation due to the effects of coagulation disturba...
Article
The amphibian temporins, amongst the smallest antimicrobial peptides (AMPs), are α-helical, amphipathic, hydrophobic and cationic and are active mainly against Gram-positive bacteria but inactive or weakly active against Gram-negative bacteria. Here, we report two novel members of the temporin family, named temporin-1Ee (FLPVIAGVLSKLFamide) and tem...
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The skin secretions of Neotropical phyllomedusine leaf frogs have proven to be a rich source of biologically active peptides, including antimicrobials. The major families of antimicrobial peptides (AMPs) reported are the dermaseptins and phylloseptins and the minor families are the dermatoxins, phylloxins, plasticins, distinctins, and medusins. Her...
Article
Full-text available
Aniridia is a congenital panocular disorder caused by the mutations of the paired box gene-6 (PAX6). To investigate the clinical characterization and the underlying genetic defect in a Chinese family with aniridia and other ocular abnormalities, we recruited the family members who underwent ophthalmic examination. Two patients in this family, the p...
Article
A simple and efficient protocol for microwave-assisted copper-catalyzed hydroxylation of aryl halides is developed. A variety of phenols can be obtained in moderate to excellent yields of up to 95%. Its application is performed to synthesize 2,3-dihydroxy-1,4-naphthoquinone, which displays significant anti-proliferation effect.
Article
Snake venom constitutes one of the most complex mixtures of naturally-occurring toxic proteins/polypeptides and a large number of these possess very profound biological activities. Disintegrins, that are commonly found in viper venoms, are low molecular weight proteins that usually contain an -Arg-Gly-Asp- (-RGD-) motif that is known to be involved...
Article
Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree o...
Article
Extensive studies on bradykinin-related peptides (BRPs) generated from plasma kininogens in representative species of various vertebrate taxa, have confirmed that many amphibian skin BRPs reflect those present in putative vertebrate predators. For example, the (Val(1), Thr(6))-bradykinin, present in the defensive skin secretions of many ranids and...
Article
Here we report the primary structure of a novel peptide, named helokinestatin-5 (VPPPLQMPLIPR), from the venom of the Gila monster (Heloderma suspectum). Helokinestatin-5 differs in structure from helokinestatin-3 by deletion of a single prolyl residue in the N-terminally located polyproline region. Two different biosynthetic precursors were consis...

Citations

... It has been demonstrated that the FDA approved antitumor drug Epothilone B could improve microtubule stability and promote α-Ability of tubulin polymerization [53]. As an EGFR and HER2 tyrosine kinase inhibitor, Lapatinib is approved by FDA to treat patients with HER2-positive breast cancer [54]. These results indicated that these potential drugs might provide novel insights into the treatment of patients with PAAD. ...
... IL-6 receptor blockers have been reported to inhibit the inflammatory response and reduce insulin resistance in DKD mice (21). In addition, by inhibiting the IL-6R/JAK2/STAT3 pathway in renal cells was able to protect the kidney in diabetic rats (22). In this study, we confirmed the promoting effect of serum IGF-1 and serum IL-6 expression levels on DKD, based on which logistic regression analysis was performed and ROC curves were constructed. ...
... In addition, other factors are responsible for the induction of the mtUPR, including the overexpression or depletion of ornithine transcarbamylase [75], as well as the overexpression of endonuclease G, which increases the load of damaged proteins [76], which leads to excess ROS [77][78][79] or pathogenic toxins, such as cyanide, produced by Pseudomonas aeruginosa [80]. Likewise, the depletion of mitochondrial import systems [81], inhibitors of mitochondrial translation, such as tetracyclines (doxycycline, minocycline, and methacycline), or chloramphenicol [45,[82][83][84][85][86][87], inhibitors of the mtETC [71,88,89], the depletion of mtDNA, and the downregulation of ribosomal protein expression also activates the mtUPR pathway [42,79]. On the other hand, itaconate, a metabolite derived from cis-aconitate, induces the mtUPR [90]. ...
... 1.385218e-03 -1.205714e-05 1.999661e-03 -4.228444e-03 -1.422853e-03 7.330554e-04 nitrite is broken down by CAT(x 15 ). Chlorophyll(x 1 ), NR(x 8 ), NiR(x 9 ), and CAT(x 15 ) collaborate with each other in C/N metabolism as well as in the growth-defenses tradeoff (Zhou et al., 2021). SPS(x 3 ) and SS(x 2 ) are both important enzymes for catalyzing sucrose synthesis in plants, however, SPS exhibiting different characteristics from sucrose SPS SS(x 2 ) was positively correlated with CAT(x 15 ), indicating that it promoted the biomass accumulation (Figure 3). ...
... The extensively studied CD95-Fc fusion proteins, for instance, represent an interesting way to inhibit CD95L. However, these chimeric proteins, compared to those used in the TNF-TNFR2 system [343], exhibit a relatively low affinity for the corresponding CD95L and far less efficacy in inhibiting death induced by ligand interaction with CD95. A possible explanation is given by the fact that the interactions between these proteins occur through a complex mechanism of oligomerization given by the association of multiple trimers of both counterparts [35,294,344]. ...
... These mechanisms eventually contribute to apoptotic cell injury and neuronal stress in DRG neurons during the early phases of diabetic sensory neuropathy. In another study contradicting Bishnoi et al. (2011), Zhang et al. (2019 reported that the varying degrees of TRPV1 expression reduction in the STZ-induced DN rat compared to the non-diabetic rat possibly explained the reduced NCV in the peripheral sciatic nerve of this rat model. The existing discrepancy is possibly due to the morphological and electrophysiological changes that occurred due to the different stages of DN in each study as Bishnoi et al. (2011) developed the early stages of DN rats (5 weeks following STZ injection) while Zhang et al. (2019) developed more severe stages of DN (8 weeks following STZ injection). ...
... These act as chaperones to prevent protein aggregation (11), stabilize myofibrils, maintain muscle fiber elasticity, allow remodeling after repeated contraction (2,12), inhibit the aggregation and precipitation of denatured proteins, and prevent loss of function under stress conditions (13). Due to the high expression of αB-crystallin in human type-I myofibers, CRYAB variants often cause selective muscle fibrosis atrophy of the trunk, spine, and limbs, such as in myofibrillar myopathy type II (14-16), dilated cardiomyopathy 1 type II (9), FIHMM (8), and multitype cataracts (17,18). Among these diseases, FIHMM is an autosomal recessive hereditary disease that generally arises in the early period as a serious muscular atrophy condition (2,4,14), with clinical manifestations including progressive stiffness of the trunk and limb muscles, flexion contracture (19), ankylosis, faint crying, dysphagia and dyspnea. ...
... Western blot results showed that it also contrib uted to the decrease in NFκB/p38MAPK signal ing pathwayrelated proteins and phosphorylated proteins. 93 By using antibiotics to reduce some intestinal bacteria in mice, it was found that normal mice taking aspirin had fewer colon tumors than ster ile mice taking aspirin. The results of the 16S rDNA technique showed that the feces samples of mice given aspirin were rich in Bifidobacterium and Lactobacillus, while Alistipes finegoldii and Bacteroides fragile were decreased. ...
... The newly developed nanoparticles (Cu@Ag NPs) have been used for the synthesis of the target compounds via one-pot condensation reaction of three components; aromatic aldehydes, cyclic-diketones, and urea in solvent free condition to obtain octahydroquinazolinone in moderate to excellent yield in short reaction time (1-5 min), Scheme 44. Under controlled microwave-assisted copper-catalyzed reaction condition, Ke and coworkers have developed new strategy for the synthesis of quinazolinone derivatives in aqueous media [73]. They have systematically improved the reaction utilizing different copper oxidation states, such as CuI, CuCl 2 , CuO, CuSO 4 , and Cu(OAc) 2 . ...
... Oxidative stress and inflammation are intertwined and affect each other. Studies have shown that ROS is the major inducement of inflammation [37], while TNF-α is the main cytokine that induces inflammation; the increase of TNF-α promotes the production of ROS and up-regulates the oxidative stress response [38]. IL-1β is the main active form of interleukin-1 (IL-1), an important pro-inflammatory cytokine in the body that participates in the regulation of the immune response and inflammatory reaction process [39]. ...