Black rockfish(Sebastes schlegelii)has evolved viviparous reproduction mode.Different from the oviparous fishes,the spermatozoa of black rockfish are stored on the surface of ovarian follicle for over four months unti...Black rockfish(Sebastes schlegelii)has evolved viviparous reproduction mode.Different from the oviparous fishes,the spermatozoa of black rockfish are stored on the surface of ovarian follicle for over four months until the egg mature in ovary,while the adaptive evolution of fertilization-related genes remains to be studied.In the present study,based on the genome and transcriptome information of black rockfish,a total of 10 hyaluronidase genes were identified by phylogenetic and sequence analyses,including hyal1,hyal2,hyal3,hyal4,hyal6 and spam1a,spam1b,spam1c and spam1d.The spam1 subfamilies,including spam1a,spam1b,spam1c and spam1d,were significantly expanded compared to other species.The adaptive evolution of hyaluronidase was further investigated by selection pressure analysis of branch model and branch site model.The results showed that only spam1 subfamily was positively selected with a large number of positive selection sites,and the evolution rate was significantly higher thanthose of other teleosts.Two positively selected sites,LYS-171 and GLY-164,were located in the neutral hyaluronidase activity domain,which was pivotal for SPAM1 to participate in enzymatic hydrolysis of the extracellular hyaluronic acid matrix and mediate acrosome reaction in mammals.Furthermore,spam1 was mainly expressed in spermatocytes,secondary spermatocytes,and spermatids of testis,whereas it was not found in metamorphic sperm and mature sperm based on the spatiotemporal expression analysis.All results indicated that spam1 might originate from the testis and might be an adaptation of viviparous trait in black rockfish.展开更多
Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.P...Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.Previously,we have shown that hyaluronidase 5(Hyal5)/Hyal7 double-knockout(dKO)mice produce significantly fewer offspring than their wild-type(WT)counterparts because of defective COC dispersal.Male infertility is mainly caused by a low sperm count.It can be further exacerbated by the deficiency of sperm hyaluronidase,which disperses the cumulus cells of the outer layer of the COC.In the current study,we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model.Our results demonstrated that a low sperm count further decreases the in vitro fertilization(IVF)rate of Hyal-deficient dKO spermatozoa.In addition,the dKO spermatozoa resulted in a fertilization rate of 12.5%upon fertilizing COCs with a thick cumulus layer,whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized.Finally,we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal.Our results suggest that a deficiency of proteins involved in fertilization,such as sperm hyal,has a vital role in fertilization.展开更多
AIM:To investigate the effect of hyaluronidase use on the quality of sub-Tenon's anaesthesia for phacoemulsification.· METHODS:This was a randomized,double-blind clinical trial which was conducted at Nikookar...AIM:To investigate the effect of hyaluronidase use on the quality of sub-Tenon's anaesthesia for phacoemulsification.· METHODS:This was a randomized,double-blind clinical trial which was conducted at Nikookari Eye Hospital for 5 months.Forty-two eyes of candidates for phacoemulsification under sub-Tenon's anaesthesia were randomly allocated to two equal groups and received either 2 mL of lidocaine 2% solution with(LH),or without(L) addition of hyaluronidase(150IU/mL).Akinesia was assessed 15 minutes after sub-Tenon's injection.Patients and surgeon's satisfaction,as well as the postoperative pain(the visual analogue scale,VAS) were investigated after operation.The contingency tables(including the Chi-square or Fisher's exact tests,when appropriate) and parametric analysis(the independent samples t test) were used for statistical analysis.· RESULTS:Complete akinesia(33.3% vs 4.8%,P =0.04),as well as the patients(85.7% vs 57.1%,P =0.04)and surgeon's satisfaction(87.5% vs 52.4%,P =0.02) were significantly more frequent in LH than in L group.The mean VAS was significantly lower in the same group(1.90±1.45 vs 3.00±1.55,P =0.04).· CONCLUSION:Addition of hyaluronidase to lidocaine solution for sub-Tenon's anesthesia significantly improves the ocular akinesia,enhances the intra-operative patients and surgeons' satisfaction,and attenuates the postoperative pain.·展开更多
Tryptophan residues in hyaluronidase (HAase) were modified by N-bromosuccinimide (NBS), the results indicated that there were eleven tryptophan residues in HAase, one of which was exposed and essential for the act...Tryptophan residues in hyaluronidase (HAase) were modified by N-bromosuccinimide (NBS), the results indicated that there were eleven tryptophan residues in HAase, one of which was exposed and essential for the activity of the enzyme. The study on fluorescence quenching showed that KI could not quench all of the fluorescence from Trp residues in HAase, while acrylamide (Acr) could quench almost all of the fluorescence from Trp residues in HAase. The collisional quenching constants (KD) of HAase at different concentrations of Acr were calculated in terms of Stern-Volmer equation. The results implied that some of the Trp residues were buried in the interior of HAase and the Trp residue on the surface of HAase was not located in the hydrophobic pocket.展开更多
Hyaluronidase enzyme (HysA) is an extracellular enzyme that is considered to be an important virulence factor for Staphylococcus aureus. We screened the production of HysA enzyme in the spent media of Egyptian clinica...Hyaluronidase enzyme (HysA) is an extracellular enzyme that is considered to be an important virulence factor for Staphylococcus aureus. We screened the production of HysA enzyme in the spent media of Egyptian clinical isolates (32 isolates) via phenotypic plate assay. We found that 75% of the isolates (24 isolates) were able to produce HysA enzyme. We designed primers for qPCR analysis of hysA mRNA expression that was derived from the alignment of hysA gene sequences of 41 strains of S. aureus. The designed primers could be used for the amplification of hysA in 79.2% of the isolates (19 isolates) that were positive for HysA production as demonstrated by phenotypic plate assay. A significant positive correlation, as indicated by Pearson correlation analysis (r = 0.84 at P < 0.001), was found between phenotypic plate assay and qPCR of mRNA expression of hysA in the investigated isolates of S. aureus. In conclusion, we analyzed for the first time hysA mRNA expression via qPCR in S. aureus. Additionally, our work showed a good agreement between the phenotypic assay of HysA production via plate assay and hysA expression in S. aureus. The qPCR analysis of this study could be used as a more reliable quantitative method for hysA expression analysis particularly in infected animal models of S. aureus.展开更多
Covalent modification of bovine testicular hyaluronidase with chondroitin sulphate led to changes in the pattern of glycation of native and modified enzyme in its reaction with neutral saccharides and N-acetylhexosami...Covalent modification of bovine testicular hyaluronidase with chondroitin sulphate led to changes in the pattern of glycation of native and modified enzyme in its reaction with neutral saccharides and N-acetylhexosamines. Thus, mono- and di-saccharides inactivated the native hyaluronidase to a greater extent than the chondroitin sulfate-modified enzyme. N-acetylhexosamine, on the opposite, inactivated the modified hyaluronidase to a greater extent than the native one. These properties made it possible to use native and modified hyaluronidase as an informative research system for in vivo measurement of the predominant type of saccharide agents in the circulation. The proposed approach was experimentally substantiated by obtained results of the study on these interactions of hyaluronidase derivatives with hyaluronan fragments and their mixture. In a model of post-ischemic perfusion of the rat limb, the effect of hyaluronidase derivatives and their components on restoration of the microcirculation were tracked using laser Doppler flowmetry. Native hyaluronidase accelerated the restoration of initial level of microcirculation, but modified enzyme was markedly inhibited by glycocalyx degradation products. N-acetylhexosamine was positioned at the reducing terminal of these products as a natural label for these glycocalyx fragments. These and other data obtained under various experimental conditions supported the participation of endothelial glycocalyx in microcirculation disturbances.展开更多
Introduction: Hyaluronidases are a group of enzymes that permit greater diffusion of fluid through the tissues. These enzymes have the ability to reduce the viscosity of hyaluronic acid and increase cellular membrane ...Introduction: Hyaluronidases are a group of enzymes that permit greater diffusion of fluid through the tissues. These enzymes have the ability to reduce the viscosity of hyaluronic acid and increase cellular membrane and blood vessel permeability. This review discusses the indication, usage, effects, and safety of hyaluronidases in obstetrics. Materials and Methods: MEDLINE/</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">PubMed and the Cochrane Library were searched using the following terms: </span><span style="font-family:Verdana;">(“hyaluronidase” [Title/Abstract]) OR (“hyaluronidases” [Title/Abstract]) AND </span><span style="font-family:Verdana;">(“therapeutic use” [Title/Abstract]) OR (“therapeutic uses” [Title/Abstract]) OR (“perineal trauma” [Title/Abstract]) OR (“perineal tear” [Title/Abstract]) OR (“cervical ripening” [Title/Abstract]). Results: This review included four randomized controlled trials (RCT) that randomized a total of 642 pregnant women and two interventional non-RCTs that included a total of 2824 pregnant women. The data from two RCTs suggested that the incidence of perineal trauma was significantly lower in the intervention (perineal hyaluronidase injection in stage two of labor) than the control group (no intervention). However, both groups did not differ significantly in the incidence of first- and second-degree tears. Similarly, no significant difference in the incidence </span><span style="font-family:Verdana;">of episiotomy was found between both groups. In one interventional non-RCT, </span><span style="font-family:Verdana;">the administration of intracervical hyaluronidase was associated with a statistically significant acceleration and shortening of labor by approximately 1.95 hours after the injection of intracervical hyaluronidase. However, it had no effect on uterine contractions or the duration of stages two and three labor. Conclusions: While it is safe, clinicians should consider patient acceptance and the effectiveness of hyaluronidase compared to conventional less invasive methods.展开更多
Aim:Hyaluronic acid(HA)is extensively used in injectable skin quality products due to its documented role in skin rejuvenation.The rapid in vivo degradation of HA by the enzyme hyaluronidase necessitates the developme...Aim:Hyaluronic acid(HA)is extensively used in injectable skin quality products due to its documented role in skin rejuvenation.The rapid in vivo degradation of HA by the enzyme hyaluronidase necessitates the development of advanced formulations to ensure the efficacy and longevity of the treatments.In this context,a novel 2.6%high molecular weight HA(H-HA)/3.2%sorbitol composition has been introduced,featuring stabilization through hydrogen bonds rather than traditional crosslinking.Methods:The stabilized composition was evaluated through two in vitro enzymatic degradation tests.In the first test,the efficiency on the gel degradation was followed by rheology and compared with two crosslinked HA products available on the market.In the second test,the effect on the gel structure of a less diluted hyaluronidase dose was followed by rheological and cohesivity measurements.Results:In vitro study demonstrates that,before its complete degradation into a liquid-like state,the stabilized composition exhibits high elasticity and cohesivity during the enzymatic degradation process,surpassing traditional crosslinked HA products.Conclusion:The stabilization provided by the sorbitol in the stabilized composition effectively enhances product properties and protects them during gel degradation.These attributes indicate significant potential for improved clinical outcomes in skin quality treatments.展开更多
The cationic charged water-soluble polyfluorenes containing 2,1,3-benzothiadiazole (BT) units (P1-3) have been synthesized and characterized. These polymers demonstrate intramolecular energy transfer from the fluorene...The cationic charged water-soluble polyfluorenes containing 2,1,3-benzothiadiazole (BT) units (P1-3) have been synthesized and characterized. These polymers demonstrate intramolecular energy transfer from the fluorene units to the BT sites when oppositely charged hyaluronan is added due to the formation of electrostatic complexes, followed by a shift in emission color from blue to green or brown. Upon adding hyaluronidase, the hyaluronan is cleaved into fragments. The relatively weak electrostatic interactions of hyaluronan fragments with polyfluorenes keep their main chains separated and energy transfer from the fluorene units to the BT sites is inefficient, and the polyfluorenes recover their blue emissions. The complexes of conjugated polymers/hyaluronan can be utilized as probes for sensitive and facile fluorescence assays for hyaluronidase. The new assay method interfaces with the aggregation and light harvesting properties of conjugated polymers.展开更多
The condensed tumor extracellular matrix(ECM)consisting of cross-linked hyaluronic acid(HA)is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penet...The condensed tumor extracellular matrix(ECM)consisting of cross-linked hyaluronic acid(HA)is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple design of a hyaluronidase(HAase)-modified layered double hydroxide(LDH)nanoplatform loaded with anticancer drug doxorubicin(DOX)for enhanced tumor penetration and augmented chemotherapy.In our approach,LDH nanodisks were synthesized via a co-precipitation method,modified with HAase by electrostatic attraction,and finally physically loaded with DOX.The formulated DOX/LDH-HAase complexes show a high DOX loading percentage of 34.2%with good colloidal stability,retain 86.1%of the enzyme activity,and release DOX in a pH-responsive manner having a faster release rate under slightly acidic tumor microenvironment than that under a physiological condition.With the catalytic activity of HAase to digest the HA nearby the cancer cells,the developed DOX/LDH-HAase complexes enable more significant uptake by cancer cells and penetration in 3-dimensional tumor spheroids than enzyme-free DOX/LDH complexes,thus displaying much better antitumor efficacy in vitro than the latter.The more significant tumor penetration and inhibition of the DOX/LDH-HAase complexes than that of the DOX/LDH complexes was further demonstrated by in vivo tumor imaging and therapeutic activity assessments.Our study suggests a unique nanomedicine platform combined with both anticancer drug and enzyme for improved tumor penetration and chemotherapy,which is promising for effective chemotherapy of different types of stroma-rich tumors.展开更多
Background Hyaluronidase (Hyase) is an enzyme which hydrolyses hyaluronan (HA), a large nonsulfated glycosaminoglycan. Several genes have been identified to code for hyaluronidases in humans. Its role has only rec...Background Hyaluronidase (Hyase) is an enzyme which hydrolyses hyaluronan (HA), a large nonsulfated glycosaminoglycan. Several genes have been identified to code for hyaluronidases in humans. Its role has only recently been underlined in the invasion of prostate cancer, colonic cancer, and breast cancer. Moreover, the findings were in agreement with some experimental results which showed that HA-derived oligosaccharides had angiogenesis-promoting activity. All these findings prompted us to investigate factors that had been characterized as putative invasive factors in different human breast cancer-derived cell lines. Methods We selected two series of human breast cancer-derived cell lines whose expression of estrogen receptors (ER) was previously published. Hyaluronidase secretion in culture medium and expression of matrix metallo-proteinase (MMP)-9, cathepsin-D (cath-D) and vascular endothelial growth factor (VEGF) by cells were determined. We also investigated cell invasiveness in the Matrigel invasion assay, and studied the capability of cancer cells to promote in vitro formation of tubules by endothelial cells. Results ER(-) cells secreted significantly more hyaluronidase (P 〈0.001) and expressed significantly more VEGF (P 〈0.01), MMP-9 (P 〈0.05) and cath-D (P 〈0.0001) than ER(+) cells. Invasion through Matrigel by ER(-) Hyase(+) cells was significantly higher than that by ER(+) Hyase(-) cells (P 〈0.05). In both cases, invasion was decreased by heparin (P 〈0.05). When ECV-304 endothelial cells were co-cultivated in millicell chambers with cancer cells, ECV-304 cells were induced to form tubules. Tubule formation was demonstrated to be more prominent with ER(-) Hyase(+) cells than with ER(+) Hyase(-) cells (P 〈0.05). Conclusion Invasive features of ER(-) breast cancer cells can be characterized in vitro by an invasive Matrigel assay, as the induction of tubule formation by ECV-304 endothelial cells, higher secretion of hyaluronidase, and higher expression of proteinases MMP-9, cath-D, and the angiogenesis promoting factor VEGF.展开更多
Leech hyaluronidase(LHyal)is a hyperactive hyaluronic acid(HA)hydrolase that belongs to the hyaluronoglu-curonidase family.Traditionally,LHyal is extracted from the heads of leeches,but the recent development of the P...Leech hyaluronidase(LHyal)is a hyperactive hyaluronic acid(HA)hydrolase that belongs to the hyaluronoglu-curonidase family.Traditionally,LHyal is extracted from the heads of leeches,but the recent development of the Pichia pastoris recombinant LHyal expression method permitted the industrial production of size-specific HA oligosaccharides.However,at present LHyal expressed by recombinant yeast strains requires laborious protein purification steps.Moreover,the enzyme is deactivated and removed after single use.To solve this problem,we developed a recyclable LHyal biocatalyst using a yeast surface display(YSD)system.After screening and charac-terization,we found that the cell wall protein Sed1p displayed stronger anchoring to the P.pastoris cell wall than other cell wall proteins.By optimizing the type and length of the linkers between LHyal and Sed1p,we increased the activity of enzymes displayed on the P.pastoris cell wall by 50.34%in flask cultures.LHyal-(GGGS)6-Sed1p activity further increased to 3.58×105 U mL−1 in fed-batch cultivation in a 5 L bioreactor.Enzymatic prop-erty analysis results revealed that the displayed LHyal-(GGGS)6-Sed1p generated the same oligosaccharides but exhibited higher thermal stability than free LHyal enzyme.Moreover,displayed LHyal-(GGGS)6-Sed1p could be recovered easily from HA hydrolysis solutions via low-speed centrifugation and could be reused at least 5 times.YSD of LHyal not only increased the utilization efficiency of the enzyme but also simplified the purification pro-cess for HA oligosaccharides.Thus,this study provides an alternative approach for the industrial preparation of LHyal and HA oligosaccharides.展开更多
Hyaluronidase(HAase)has been regarded as one of the potential cancer biomarkers.In this study,a novel enzyme-responded controlled release electrochemical biosensor has been constructed for HAase detection.Methylene bl...Hyaluronidase(HAase)has been regarded as one of the potential cancer biomarkers.In this study,a novel enzyme-responded controlled release electrochemical biosensor has been constructed for HAase detection.Methylene blue(MB)can be adsorbed on hyaluronic acid(HA)to form macromolecular HA–MB complex first through electrostatic interaction between anionic HA and positively charged MB.The prepared complex cannot be filtered out through centrifugal ultrafiltration,and small electrochemical signal can be recorded from the ultrafiltrate.With the help of HAase,HA–MB complex can be cleaved into small pieces through enzyme digestion.The small pieces of HA–MB complex can be easily released from the macromolecular HA–MB complex to the ultrafiltrate by centrifugal ultrafiltration.Then,the enhanced electrochemical signal from MB can be detected in the above-mentioned ultrafiltrate.The enhanced diff erential pulse voltammetric response of the system has a linear relationship with HAase concentration in the range of 4.0–60 U·mL^(-1),with the limit of detection of 0.28 U·mL^(-1).The developed strategy has been successfully applied to detect HAase activity in urine samples.展开更多
The study was prospective, randomized and controlled. It includes 3 parts: (1) clinical study of hyaluronidase (HD) on cervical ripening; (2) action mechanism of HD (experimental study); and (3) effect of cervix colla...The study was prospective, randomized and controlled. It includes 3 parts: (1) clinical study of hyaluronidase (HD) on cervical ripening; (2) action mechanism of HD (experimental study); and (3) effect of cervix collagen on cervical dilatation in term labor. According to the results of preliminary study, HD was selected as ripening agent, its dosage and administration method were investigated previously.展开更多
Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the...Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.展开更多
Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and p...Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg~(-l).d~(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg~(-l)-d~(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)展开更多
Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation a...Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, pre-vention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.展开更多
Natural polyphenol has been widely believed to be effective in allergy remission. Currently, most of the natural poly- phenol products come from terrestrial sources such as tea, grape seeds among others, and few polyp...Natural polyphenol has been widely believed to be effective in allergy remission. Currently, most of the natural poly- phenol products come from terrestrial sources such as tea, grape seeds among others, and few polyphenols have been developed from algae for their anti-allergic activity. The aim of the study was to screen some commercial seaweed for natural extracts with anti-al- lergic activity. Five algae including Laminaria japonica, Porphyra sp., Spirulina platensis, Chlorella pyrenoidosa and Scytosiphon sp were extracted with ethanol, and the extracts were evaluated for total polyphenol contents and anti-allergic activity with the hyalu- ronidase inhibition assay. Results showed that the total polyphenol contents in the ethanol extracts ranged from 1.67% to 8.47%, while the highest was found in the extract from Scytosiphon sp. Hyaluronidase inhibition assay showed that the extracts from Scyto- siphon sp. had the lowest IC50, 0.67 mg mL-1, while Chlorella pyrenoidosa extract had the highest IC50, 15.07 mg mL-1. The anti-allergic activity of Scytosiphon sp. extract was even higher than the typical anti-allergic drug Disodium Cromoglycate (DSCG) (IC50=1.13 mg mL-1), and was similar with natural polyphenol from Epigallocatechin gallate (EGCG) (IC50 = 0.56 mg mL-l). These results indicated that the ethanol extract of Scytosiphon sp. contains a high concentration of polyphenol with high anti-allergic activ- ity. Potentially Scytosiphon sp. can be developed to a natural anti-allergic compound for allergy remission.展开更多
Ethanol extracts of brown seaweeds from Pakistan and China were isolated and compared for their antiallergenic activities. They included Sargassum tennerimum (ST) and Sargassum cervicorne (SC) from Pakistan, and Sarga...Ethanol extracts of brown seaweeds from Pakistan and China were isolated and compared for their antiallergenic activities. They included Sargassum tennerimum (ST) and Sargassum cervicorne (SC) from Pakistan, and Sargassum gramini- folium turn (SG), Sargassum thunbergii (STH), and Laminaria japonica (LJ) from China. The ethanol extracts of these brown seaweeds were optimized at 85% (v/v) ethanol for the maximum yield of phlorotannin, an inhibitor against hyaluronidase. Total phlorotannins contained in the crude extracts were measured as 1.71% (SG), 0.74% (STH), 0.97% (LJ), 3.30% (SC), and 5.06% (ST). The 50% inhibitory concentrations (IC50) of Pakistani SC and ST were 109.5 and 21 μg/ml, respectively, lower than those of Chinese SG, STH, and LJ (134, 269, and 148 μg/ml, respectively). An antiallergic drug, disodium cromoglycate (DSCG), had an IC50=39 μg/ml, and a natural inhibitor of hyaluronidase, catechin, had an IC50=20 μg/ml. The IC50 of ST extract was found similar to that of catechin (21 vs 20 μg/ml) and lower than that of DSCG (21 vs 39 μg/ml). This suggests that ST is a potent inhibitor of hyaluronidase, indicating a promising future development of natural antiallergic medicines or functional foods.展开更多
Bacterial infection and insufficient osseointegration are critical factors affecting the long-term success of titanium-based implants.Unfortunately,the direct application of antibiotic on Ti implants easily leads to p...Bacterial infection and insufficient osseointegration are critical factors affecting the long-term success of titanium-based implants.Unfortunately,the direct application of antibiotic on Ti implants easily leads to poor cytocompatibility,as well as the production of drug-resistant bacteria.So,in this work,we designed a prospective antibacterial strategy by combining photothermal and ciprofloxacin(CIP).The synergistic effect of photothermal and antibiotic may provide an effective bacteriostatic efficacy without sacrificing osteogenesis at a mild condition of moderate temperature and less antibiotic.Herein,CIP was loaded into mesoporous polydopamine(MPDA)nanoparticles(MPDA@CIP),which were anchored on the surface of titanium and finally covered with sodium hyaluronate-catechol(HAc)coating.The hydrophilic HAc layer could inhibit the early adhesion of bacteria,and some bacteria could secrete bacterial hyaluronidase to accelerate the degradation of HAc.This enabled smart enzyme-triggered release of antimicrobials at the site of infection on-demand and avoided unwanted side effects on normal tissues.In addition,NIR light irradiation had a positive influence on both CIP release and MPDA nanoparticle’s photothermal effect.Moreover,before anchoring MPDA@CIP,by the construction of hydroxyapatite microstructure on Ti sur-face with micro-arc oxidation and alkali heat treatment,the ability of bone formation of Ti could be promoted also.Both in vitro as well as in vivo assays demonstrated that functional Ti has an excellent antibacterial effect and osteogenic ability.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32273133,31970492).
文摘Black rockfish(Sebastes schlegelii)has evolved viviparous reproduction mode.Different from the oviparous fishes,the spermatozoa of black rockfish are stored on the surface of ovarian follicle for over four months until the egg mature in ovary,while the adaptive evolution of fertilization-related genes remains to be studied.In the present study,based on the genome and transcriptome information of black rockfish,a total of 10 hyaluronidase genes were identified by phylogenetic and sequence analyses,including hyal1,hyal2,hyal3,hyal4,hyal6 and spam1a,spam1b,spam1c and spam1d.The spam1 subfamilies,including spam1a,spam1b,spam1c and spam1d,were significantly expanded compared to other species.The adaptive evolution of hyaluronidase was further investigated by selection pressure analysis of branch model and branch site model.The results showed that only spam1 subfamily was positively selected with a large number of positive selection sites,and the evolution rate was significantly higher thanthose of other teleosts.Two positively selected sites,LYS-171 and GLY-164,were located in the neutral hyaluronidase activity domain,which was pivotal for SPAM1 to participate in enzymatic hydrolysis of the extracellular hyaluronic acid matrix and mediate acrosome reaction in mammals.Furthermore,spam1 was mainly expressed in spermatocytes,secondary spermatocytes,and spermatids of testis,whereas it was not found in metamorphic sperm and mature sperm based on the spatiotemporal expression analysis.All results indicated that spam1 might originate from the testis and might be an adaptation of viviparous trait in black rockfish.
基金supported by the KRIBB Research Initiative Program(KGM4252122)the National Research Foundation(2018M2A9Hl078340)the National Research Foundation of Korea Grant funded by the Korean Government(NRF-2020R111A3072358).
文摘Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.Previously,we have shown that hyaluronidase 5(Hyal5)/Hyal7 double-knockout(dKO)mice produce significantly fewer offspring than their wild-type(WT)counterparts because of defective COC dispersal.Male infertility is mainly caused by a low sperm count.It can be further exacerbated by the deficiency of sperm hyaluronidase,which disperses the cumulus cells of the outer layer of the COC.In the current study,we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model.Our results demonstrated that a low sperm count further decreases the in vitro fertilization(IVF)rate of Hyal-deficient dKO spermatozoa.In addition,the dKO spermatozoa resulted in a fertilization rate of 12.5%upon fertilizing COCs with a thick cumulus layer,whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized.Finally,we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal.Our results suggest that a deficiency of proteins involved in fertilization,such as sperm hyal,has a vital role in fertilization.
文摘AIM:To investigate the effect of hyaluronidase use on the quality of sub-Tenon's anaesthesia for phacoemulsification.· METHODS:This was a randomized,double-blind clinical trial which was conducted at Nikookari Eye Hospital for 5 months.Forty-two eyes of candidates for phacoemulsification under sub-Tenon's anaesthesia were randomly allocated to two equal groups and received either 2 mL of lidocaine 2% solution with(LH),or without(L) addition of hyaluronidase(150IU/mL).Akinesia was assessed 15 minutes after sub-Tenon's injection.Patients and surgeon's satisfaction,as well as the postoperative pain(the visual analogue scale,VAS) were investigated after operation.The contingency tables(including the Chi-square or Fisher's exact tests,when appropriate) and parametric analysis(the independent samples t test) were used for statistical analysis.· RESULTS:Complete akinesia(33.3% vs 4.8%,P =0.04),as well as the patients(85.7% vs 57.1%,P =0.04)and surgeon's satisfaction(87.5% vs 52.4%,P =0.02) were significantly more frequent in LH than in L group.The mean VAS was significantly lower in the same group(1.90±1.45 vs 3.00±1.55,P =0.04).· CONCLUSION:Addition of hyaluronidase to lidocaine solution for sub-Tenon's anesthesia significantly improves the ocular akinesia,enhances the intra-operative patients and surgeons' satisfaction,and attenuates the postoperative pain.·
文摘Tryptophan residues in hyaluronidase (HAase) were modified by N-bromosuccinimide (NBS), the results indicated that there were eleven tryptophan residues in HAase, one of which was exposed and essential for the activity of the enzyme. The study on fluorescence quenching showed that KI could not quench all of the fluorescence from Trp residues in HAase, while acrylamide (Acr) could quench almost all of the fluorescence from Trp residues in HAase. The collisional quenching constants (KD) of HAase at different concentrations of Acr were calculated in terms of Stern-Volmer equation. The results implied that some of the Trp residues were buried in the interior of HAase and the Trp residue on the surface of HAase was not located in the hydrophobic pocket.
文摘Hyaluronidase enzyme (HysA) is an extracellular enzyme that is considered to be an important virulence factor for Staphylococcus aureus. We screened the production of HysA enzyme in the spent media of Egyptian clinical isolates (32 isolates) via phenotypic plate assay. We found that 75% of the isolates (24 isolates) were able to produce HysA enzyme. We designed primers for qPCR analysis of hysA mRNA expression that was derived from the alignment of hysA gene sequences of 41 strains of S. aureus. The designed primers could be used for the amplification of hysA in 79.2% of the isolates (19 isolates) that were positive for HysA production as demonstrated by phenotypic plate assay. A significant positive correlation, as indicated by Pearson correlation analysis (r = 0.84 at P < 0.001), was found between phenotypic plate assay and qPCR of mRNA expression of hysA in the investigated isolates of S. aureus. In conclusion, we analyzed for the first time hysA mRNA expression via qPCR in S. aureus. Additionally, our work showed a good agreement between the phenotypic assay of HysA production via plate assay and hysA expression in S. aureus. The qPCR analysis of this study could be used as a more reliable quantitative method for hysA expression analysis particularly in infected animal models of S. aureus.
文摘Covalent modification of bovine testicular hyaluronidase with chondroitin sulphate led to changes in the pattern of glycation of native and modified enzyme in its reaction with neutral saccharides and N-acetylhexosamines. Thus, mono- and di-saccharides inactivated the native hyaluronidase to a greater extent than the chondroitin sulfate-modified enzyme. N-acetylhexosamine, on the opposite, inactivated the modified hyaluronidase to a greater extent than the native one. These properties made it possible to use native and modified hyaluronidase as an informative research system for in vivo measurement of the predominant type of saccharide agents in the circulation. The proposed approach was experimentally substantiated by obtained results of the study on these interactions of hyaluronidase derivatives with hyaluronan fragments and their mixture. In a model of post-ischemic perfusion of the rat limb, the effect of hyaluronidase derivatives and their components on restoration of the microcirculation were tracked using laser Doppler flowmetry. Native hyaluronidase accelerated the restoration of initial level of microcirculation, but modified enzyme was markedly inhibited by glycocalyx degradation products. N-acetylhexosamine was positioned at the reducing terminal of these products as a natural label for these glycocalyx fragments. These and other data obtained under various experimental conditions supported the participation of endothelial glycocalyx in microcirculation disturbances.
文摘Introduction: Hyaluronidases are a group of enzymes that permit greater diffusion of fluid through the tissues. These enzymes have the ability to reduce the viscosity of hyaluronic acid and increase cellular membrane and blood vessel permeability. This review discusses the indication, usage, effects, and safety of hyaluronidases in obstetrics. Materials and Methods: MEDLINE/</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">PubMed and the Cochrane Library were searched using the following terms: </span><span style="font-family:Verdana;">(“hyaluronidase” [Title/Abstract]) OR (“hyaluronidases” [Title/Abstract]) AND </span><span style="font-family:Verdana;">(“therapeutic use” [Title/Abstract]) OR (“therapeutic uses” [Title/Abstract]) OR (“perineal trauma” [Title/Abstract]) OR (“perineal tear” [Title/Abstract]) OR (“cervical ripening” [Title/Abstract]). Results: This review included four randomized controlled trials (RCT) that randomized a total of 642 pregnant women and two interventional non-RCTs that included a total of 2824 pregnant women. The data from two RCTs suggested that the incidence of perineal trauma was significantly lower in the intervention (perineal hyaluronidase injection in stage two of labor) than the control group (no intervention). However, both groups did not differ significantly in the incidence of first- and second-degree tears. Similarly, no significant difference in the incidence </span><span style="font-family:Verdana;">of episiotomy was found between both groups. In one interventional non-RCT, </span><span style="font-family:Verdana;">the administration of intracervical hyaluronidase was associated with a statistically significant acceleration and shortening of labor by approximately 1.95 hours after the injection of intracervical hyaluronidase. However, it had no effect on uterine contractions or the duration of stages two and three labor. Conclusions: While it is safe, clinicians should consider patient acceptance and the effectiveness of hyaluronidase compared to conventional less invasive methods.
基金Kylane Laboratoires SA provided logistical and financial support for the conduct of this study.
文摘Aim:Hyaluronic acid(HA)is extensively used in injectable skin quality products due to its documented role in skin rejuvenation.The rapid in vivo degradation of HA by the enzyme hyaluronidase necessitates the development of advanced formulations to ensure the efficacy and longevity of the treatments.In this context,a novel 2.6%high molecular weight HA(H-HA)/3.2%sorbitol composition has been introduced,featuring stabilization through hydrogen bonds rather than traditional crosslinking.Methods:The stabilized composition was evaluated through two in vitro enzymatic degradation tests.In the first test,the efficiency on the gel degradation was followed by rheology and compared with two crosslinked HA products available on the market.In the second test,the effect on the gel structure of a less diluted hyaluronidase dose was followed by rheological and cohesivity measurements.Results:In vitro study demonstrates that,before its complete degradation into a liquid-like state,the stabilized composition exhibits high elasticity and cohesivity during the enzymatic degradation process,surpassing traditional crosslinked HA products.Conclusion:The stabilization provided by the sorbitol in the stabilized composition effectively enhances product properties and protects them during gel degradation.These attributes indicate significant potential for improved clinical outcomes in skin quality treatments.
基金Supported by the "100 Talents" Program of Chinese Academy of Sciencesthe Na-tional Natural Science Foundation of China (Grant Nos. 20725308 & 20721061)973 Project (Grant Nos. 2006CB806200 & 2006CB932100)
文摘The cationic charged water-soluble polyfluorenes containing 2,1,3-benzothiadiazole (BT) units (P1-3) have been synthesized and characterized. These polymers demonstrate intramolecular energy transfer from the fluorene units to the BT sites when oppositely charged hyaluronan is added due to the formation of electrostatic complexes, followed by a shift in emission color from blue to green or brown. Upon adding hyaluronidase, the hyaluronan is cleaved into fragments. The relatively weak electrostatic interactions of hyaluronan fragments with polyfluorenes keep their main chains separated and energy transfer from the fluorene units to the BT sites is inefficient, and the polyfluorenes recover their blue emissions. The complexes of conjugated polymers/hyaluronan can be utilized as probes for sensitive and facile fluorescence assays for hyaluronidase. The new assay method interfaces with the aggregation and light harvesting properties of conjugated polymers.
基金This work was supported by the National Natural Science Foundation of China(81761148028,21773026,82001830)the National Key R&D Program(2017YFE0196200)+1 种基金the Science and Technology Commission of Shanghai Municipality(19XD1400100,19410740-200,20520710300)and the Shanghai Education Commission through the Shanghai Leading Talents Program.
文摘The condensed tumor extracellular matrix(ECM)consisting of cross-linked hyaluronic acid(HA)is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple design of a hyaluronidase(HAase)-modified layered double hydroxide(LDH)nanoplatform loaded with anticancer drug doxorubicin(DOX)for enhanced tumor penetration and augmented chemotherapy.In our approach,LDH nanodisks were synthesized via a co-precipitation method,modified with HAase by electrostatic attraction,and finally physically loaded with DOX.The formulated DOX/LDH-HAase complexes show a high DOX loading percentage of 34.2%with good colloidal stability,retain 86.1%of the enzyme activity,and release DOX in a pH-responsive manner having a faster release rate under slightly acidic tumor microenvironment than that under a physiological condition.With the catalytic activity of HAase to digest the HA nearby the cancer cells,the developed DOX/LDH-HAase complexes enable more significant uptake by cancer cells and penetration in 3-dimensional tumor spheroids than enzyme-free DOX/LDH complexes,thus displaying much better antitumor efficacy in vitro than the latter.The more significant tumor penetration and inhibition of the DOX/LDH-HAase complexes than that of the DOX/LDH complexes was further demonstrated by in vivo tumor imaging and therapeutic activity assessments.Our study suggests a unique nanomedicine platform combined with both anticancer drug and enzyme for improved tumor penetration and chemotherapy,which is promising for effective chemotherapy of different types of stroma-rich tumors.
文摘Background Hyaluronidase (Hyase) is an enzyme which hydrolyses hyaluronan (HA), a large nonsulfated glycosaminoglycan. Several genes have been identified to code for hyaluronidases in humans. Its role has only recently been underlined in the invasion of prostate cancer, colonic cancer, and breast cancer. Moreover, the findings were in agreement with some experimental results which showed that HA-derived oligosaccharides had angiogenesis-promoting activity. All these findings prompted us to investigate factors that had been characterized as putative invasive factors in different human breast cancer-derived cell lines. Methods We selected two series of human breast cancer-derived cell lines whose expression of estrogen receptors (ER) was previously published. Hyaluronidase secretion in culture medium and expression of matrix metallo-proteinase (MMP)-9, cathepsin-D (cath-D) and vascular endothelial growth factor (VEGF) by cells were determined. We also investigated cell invasiveness in the Matrigel invasion assay, and studied the capability of cancer cells to promote in vitro formation of tubules by endothelial cells. Results ER(-) cells secreted significantly more hyaluronidase (P 〈0.001) and expressed significantly more VEGF (P 〈0.01), MMP-9 (P 〈0.05) and cath-D (P 〈0.0001) than ER(+) cells. Invasion through Matrigel by ER(-) Hyase(+) cells was significantly higher than that by ER(+) Hyase(-) cells (P 〈0.05). In both cases, invasion was decreased by heparin (P 〈0.05). When ECV-304 endothelial cells were co-cultivated in millicell chambers with cancer cells, ECV-304 cells were induced to form tubules. Tubule formation was demonstrated to be more prominent with ER(-) Hyase(+) cells than with ER(+) Hyase(-) cells (P 〈0.05). Conclusion Invasive features of ER(-) breast cancer cells can be characterized in vitro by an invasive Matrigel assay, as the induction of tubule formation by ECV-304 endothelial cells, higher secretion of hyaluronidase, and higher expression of proteinases MMP-9, cath-D, and the angiogenesis promoting factor VEGF.
基金supported by the National Natural Science Foundation of China(32000058)the Jiangsu Province Natural Science Fund for Distinguished Young Scholars(BK20200025)the National Key Research and Development Program of China(2021YFC2103100).
文摘Leech hyaluronidase(LHyal)is a hyperactive hyaluronic acid(HA)hydrolase that belongs to the hyaluronoglu-curonidase family.Traditionally,LHyal is extracted from the heads of leeches,but the recent development of the Pichia pastoris recombinant LHyal expression method permitted the industrial production of size-specific HA oligosaccharides.However,at present LHyal expressed by recombinant yeast strains requires laborious protein purification steps.Moreover,the enzyme is deactivated and removed after single use.To solve this problem,we developed a recyclable LHyal biocatalyst using a yeast surface display(YSD)system.After screening and charac-terization,we found that the cell wall protein Sed1p displayed stronger anchoring to the P.pastoris cell wall than other cell wall proteins.By optimizing the type and length of the linkers between LHyal and Sed1p,we increased the activity of enzymes displayed on the P.pastoris cell wall by 50.34%in flask cultures.LHyal-(GGGS)6-Sed1p activity further increased to 3.58×105 U mL−1 in fed-batch cultivation in a 5 L bioreactor.Enzymatic prop-erty analysis results revealed that the displayed LHyal-(GGGS)6-Sed1p generated the same oligosaccharides but exhibited higher thermal stability than free LHyal enzyme.Moreover,displayed LHyal-(GGGS)6-Sed1p could be recovered easily from HA hydrolysis solutions via low-speed centrifugation and could be reused at least 5 times.YSD of LHyal not only increased the utilization efficiency of the enzyme but also simplified the purification pro-cess for HA oligosaccharides.Thus,this study provides an alternative approach for the industrial preparation of LHyal and HA oligosaccharides.
基金financially supported by National Sciences Foundation of China(21575025,21575027)the cooperative project of production and study in University of Fujian Province(2018Y4007)STS Key Project of Fujian Province(2017T3007)
文摘Hyaluronidase(HAase)has been regarded as one of the potential cancer biomarkers.In this study,a novel enzyme-responded controlled release electrochemical biosensor has been constructed for HAase detection.Methylene blue(MB)can be adsorbed on hyaluronic acid(HA)to form macromolecular HA–MB complex first through electrostatic interaction between anionic HA and positively charged MB.The prepared complex cannot be filtered out through centrifugal ultrafiltration,and small electrochemical signal can be recorded from the ultrafiltrate.With the help of HAase,HA–MB complex can be cleaved into small pieces through enzyme digestion.The small pieces of HA–MB complex can be easily released from the macromolecular HA–MB complex to the ultrafiltrate by centrifugal ultrafiltration.Then,the enhanced electrochemical signal from MB can be detected in the above-mentioned ultrafiltrate.The enhanced diff erential pulse voltammetric response of the system has a linear relationship with HAase concentration in the range of 4.0–60 U·mL^(-1),with the limit of detection of 0.28 U·mL^(-1).The developed strategy has been successfully applied to detect HAase activity in urine samples.
文摘The study was prospective, randomized and controlled. It includes 3 parts: (1) clinical study of hyaluronidase (HD) on cervical ripening; (2) action mechanism of HD (experimental study); and (3) effect of cervix collagen on cervical dilatation in term labor. According to the results of preliminary study, HD was selected as ripening agent, its dosage and administration method were investigated previously.
基金financially supported by the National Key Research and Development Program of China(No.2021YFC2100900)the National Natural Science Foundation of China(No.32171261)+1 种基金the Taishan Industry Leading Talent of Shandong Province(No.tscx202211017)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_2575).
文摘Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.
文摘Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg~(-l).d~(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg~(-l)-d~(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)
文摘Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, pre-vention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.
基金financially supported by Shandong Province Young and Middle-Aged Scientists Research Awards Fund(BS2011HZ020)the National Natural Science Foundation of China(No.31371730)Program for Changjiang Scholars and Innovative Research Team in University
文摘Natural polyphenol has been widely believed to be effective in allergy remission. Currently, most of the natural poly- phenol products come from terrestrial sources such as tea, grape seeds among others, and few polyphenols have been developed from algae for their anti-allergic activity. The aim of the study was to screen some commercial seaweed for natural extracts with anti-al- lergic activity. Five algae including Laminaria japonica, Porphyra sp., Spirulina platensis, Chlorella pyrenoidosa and Scytosiphon sp were extracted with ethanol, and the extracts were evaluated for total polyphenol contents and anti-allergic activity with the hyalu- ronidase inhibition assay. Results showed that the total polyphenol contents in the ethanol extracts ranged from 1.67% to 8.47%, while the highest was found in the extract from Scytosiphon sp. Hyaluronidase inhibition assay showed that the extracts from Scyto- siphon sp. had the lowest IC50, 0.67 mg mL-1, while Chlorella pyrenoidosa extract had the highest IC50, 15.07 mg mL-1. The anti-allergic activity of Scytosiphon sp. extract was even higher than the typical anti-allergic drug Disodium Cromoglycate (DSCG) (IC50=1.13 mg mL-1), and was similar with natural polyphenol from Epigallocatechin gallate (EGCG) (IC50 = 0.56 mg mL-l). These results indicated that the ethanol extract of Scytosiphon sp. contains a high concentration of polyphenol with high anti-allergic activ- ity. Potentially Scytosiphon sp. can be developed to a natural anti-allergic compound for allergy remission.
基金Project supported by the Hi-Tech Research and Development Program(863)of China(No.2006AA09Z427)the National Natural Science Foundation of China(Nos.30800859 and 30871948)
文摘Ethanol extracts of brown seaweeds from Pakistan and China were isolated and compared for their antiallergenic activities. They included Sargassum tennerimum (ST) and Sargassum cervicorne (SC) from Pakistan, and Sargassum gramini- folium turn (SG), Sargassum thunbergii (STH), and Laminaria japonica (LJ) from China. The ethanol extracts of these brown seaweeds were optimized at 85% (v/v) ethanol for the maximum yield of phlorotannin, an inhibitor against hyaluronidase. Total phlorotannins contained in the crude extracts were measured as 1.71% (SG), 0.74% (STH), 0.97% (LJ), 3.30% (SC), and 5.06% (ST). The 50% inhibitory concentrations (IC50) of Pakistani SC and ST were 109.5 and 21 μg/ml, respectively, lower than those of Chinese SG, STH, and LJ (134, 269, and 148 μg/ml, respectively). An antiallergic drug, disodium cromoglycate (DSCG), had an IC50=39 μg/ml, and a natural inhibitor of hyaluronidase, catechin, had an IC50=20 μg/ml. The IC50 of ST extract was found similar to that of catechin (21 vs 20 μg/ml) and lower than that of DSCG (21 vs 39 μg/ml). This suggests that ST is a potent inhibitor of hyaluronidase, indicating a promising future development of natural antiallergic medicines or functional foods.
基金financially supported by the National Natu-ral Science Foundation of China (Nos.32071334,51825302 and 21734002)the Natural Science Foundation of Chongqing (Nos.cstc2021jcyj-cxttX0002 and cstc2019jscx-msxmX0160).
文摘Bacterial infection and insufficient osseointegration are critical factors affecting the long-term success of titanium-based implants.Unfortunately,the direct application of antibiotic on Ti implants easily leads to poor cytocompatibility,as well as the production of drug-resistant bacteria.So,in this work,we designed a prospective antibacterial strategy by combining photothermal and ciprofloxacin(CIP).The synergistic effect of photothermal and antibiotic may provide an effective bacteriostatic efficacy without sacrificing osteogenesis at a mild condition of moderate temperature and less antibiotic.Herein,CIP was loaded into mesoporous polydopamine(MPDA)nanoparticles(MPDA@CIP),which were anchored on the surface of titanium and finally covered with sodium hyaluronate-catechol(HAc)coating.The hydrophilic HAc layer could inhibit the early adhesion of bacteria,and some bacteria could secrete bacterial hyaluronidase to accelerate the degradation of HAc.This enabled smart enzyme-triggered release of antimicrobials at the site of infection on-demand and avoided unwanted side effects on normal tissues.In addition,NIR light irradiation had a positive influence on both CIP release and MPDA nanoparticle’s photothermal effect.Moreover,before anchoring MPDA@CIP,by the construction of hydroxyapatite microstructure on Ti sur-face with micro-arc oxidation and alkali heat treatment,the ability of bone formation of Ti could be promoted also.Both in vitro as well as in vivo assays demonstrated that functional Ti has an excellent antibacterial effect and osteogenic ability.