Biomedical subjects

Yan Chen

Publications and source records attributed to Yan Chen.

At least 289 records · Page 16Linked to original sources

PubMed2002

Inhibition of doxorubicin chronic toxicity in catalase-overexpressing transgenic mouse hearts.

Catalase is an important antioxidant enzyme, which has been shown to provide cardiac protection from acute toxicity induced by doxorubicin, a most effective anticancer agent. Because cumulative dose-dependent chronic cardiomyopathy due to a long-term administration of doxorubicin is a significant clinical problem, the present study was undertaken to test the hypothesis that catalase also provides protection against doxorubicin chronic cardiotoxicity. Transgenic mice containing cardiac catalase activities of 15-, 60-, or 100-fold higher than normal and nontransgenic controls were treated with doxorubicin in a cumulative dose of 45 mg/kg in five equal iv injections (9 mg/kg every other week) over a period of 10 weeks. On the second day after the last injection, the mice were sacrificed for analysis of cardiotoxicity. As compared to nontransgenic controls, doxorubicin-reduced body weight gain was significantly inhibited in the transgenic mice. There were 15% mortality in nontransgenic mice, but no mortality was observed in transgenic mice during the course of treatment. Light microscopic examination revealed that doxorubicin-induced myocardial morphological changes were markedly suppressed in the transgenic mice in an activity-dependent fashion. Under electron microscopy, extensive sarcoplasmic vacuolization and severe disruption of mitochondrial fine structure were observed in nontransgenic cardiomyocytes, but all markedly suppressed in the transgenic mice. The results indicate that catalase elevation in the heart prevents doxorubicin chronic cardiomyopathy.

Animals↗

PubMed2002

The cyclopentenone product of lipid peroxidation, 15-A(2t)-isoprostane (8-isoprostaglandin A(2)), is efficiently conjugated with glutathione by human and rat glutathione transferase A4-4.

Glutathione transferases (GSTs) are a large family of enzymes that can be divided into different classes based on structure. There has been considerable interest in the ability of GSTs to conjugate and inactivate endogenously derived reactive lipid peroxidation products that contain alpha,beta-unsaturated carbonyl moieties such as 4-hydroxyalkenals. One enzyme with prominent activity toward these substrates is human GST A4-4. Recently, we described a novel series of compounds termed A(2)/J(2)-isoprostanes (IsoPs) that are formed endogenously in humans from the free radical-initiated peroxidation of arachidonic acid. These compounds contain alpha,beta-unsaturated carbonyl groups and have structures similar to cyclooxygenase-derived PGA(2) and PGJ(2). Because of their chemical reactivity, these compounds may mediate tissue injury associated with oxidant stress. Herein, we report that the A-ring IsoP 15-A(2t)-IsoP (8-iso-PGA(2)) is efficiently conjugated to glutathione (GSH) by human GST A4-4 with a k(cat)/K(m) value of >200 s(-)(1) mM(-)(1). The k(cat)/K(m) value for conjugation of 15-A(2t)-IsoP by the homologous rat GST A4-4 is >2000 s(-)(1) mM(-)(1). Similar high enzyme activities were observed when PGA(2) was used as a substrate. In contrast, the human GSTs A1-1, M1-1, M2-2, P1-1, and T1-1 and rat GST T2-2 did not significantly metabolize 15-A(2t)-IsoP. These studies have therefore defined a potentially important route by which cyclopentenone IsoPs are metabolized that may serve as a mechanism for the inactivation of these highly reactive compounds.

Animals↗

PubMed2002

Get effective polyclonal antisera in one month.

According to the traditional immunization procedure, after the first injection of the sample A (emulsion of aimed antigen and Freund's complete adjuvant) to immunize rabbit, successive injections of the sample B (emulsion of aimed antigen and Freund's incomplete adjuvant) were followed every 2-4 weeks. In general, high titer of the corresponding polyclonal antisera will be observed after 4-5 injections of sample B in 3-4 months. This report presents a simply modified procedure that was able to stimulate the antisera formation in one month and achieve enough avidity to satisfy either Western blot or immunohistochemistry analysis. It just applied an additional injection of the sample A to the rabbit at the 3rd day after the primary immunization injection. You could gain the high titer of the antisera right after the first sample B injection in one month. This method has produced the desired results in three different recombinant antigens with different molecular weight (5.9 KD-55 KD) expressed from prokaryotic or eukaryotic cells.

Animals↗

PubMed2002

Distribution of carbon monoxide-producing neurons in human colon and in Hirschsprung's disease patients.

Hirschsprung's disease (HSCR) is characterized by the absence of ganglion cells and impaired relaxation of the gut. Nitric oxide (NO) and, more recently, carbon monoxide (CO) have been identified as inhibitory neurotransmitters causing relaxation. A deficiency in NO has been reported in aganglionic gut; we hypothesized that CO could also be involved in impaired gut motility in HSCR. The aim of the study was to determine the distribution of CO-and NO-producing enzymes in the normal and aganglionic gut. We performed laser capture microdissection, reverse transcription-polymerase chain reaction, and immunohistochemistry on colon biopsies of normal controls (n = 9) and patients with HSCR (n = 10). The mRNA expression of heme oxygenase-2 (HO-2), immunoreactivities of HO-2 and NO synthase, was determined and compared. Results show a high level of expression of HO-2 mRNA localized in the myenteric plexus. Expression of HO-2 mRNA was also detected in the mucosa, submucosa, and muscular layer. Down-regulation of HO-2 mRNA expression was detected in the aganglionic colon. Immunoreactivities of HO-2 and NO synthase were localized mainly to the ganglion plexus and to nerve fibers within the muscle in the control colons and normoganglionic colons. HO-2-containing neurons were more abundant than NO synthase-containing neurons in the myenteric plexus. Nearly all of the NO synthase-containing neurons also contained HO-2. HO-2 and NO synthase were selectively absent in the myenteric and submucosal regions and in the muscle of the aganglionic colon. Our findings suggest involvement of both CO and NO in the pathophysiology of HSCR.

Carbon Monoxide↗

PubMed2002

Anterograde projections of the motorcortical tongue area in the saddle-back tamarin (Saguinus fuscicollis).

In the New World monkey Saguinus fuscicollis, the anterograde projections of the motorcortical tongue area were studied. Three animals were analyzed. In two, biotin dextran amine was used as tracer; in the third, Phaseolus vulgaris leucoagglutinin was used. Identification of the tongue area was carried out by electrical brain stimulation. Intracortical projections were found into the neighboring primary motor cortex, ventral premotor cortex, frontoopercular cortex, and primary and secondary somatosensory cortex. Projections also ended in the ventrolateral prefrontal cortex, orbital cortex, supplementary motor area, anterior cingulate cortex and agranular as well as granular insula. In addition, weaker labeling was found in the inferior and dorsal parietal cortex, and perirhinal and inferotemporal cortex. Subcortically, there was a heavy projection into the ventral putamen, a moderate projection into the caudate nucleus and claustrum, and a weak projection into the anterior, central and lateral amygdala. In the thalamus, terminal labeling was found in the nuclei ventralis posterior medialis, ventralis lateralis, reticularis, centralis lateralis, medialis dorsalis, pulvinaris oralis, centrum medianum, reuniens and suprageniculatus in an order of intensity. Subthalamically, weak projections could be traced into the zona incerta and lateral hypothalamus. In the midbrain, labeling was found in the deep layers of the colliculus superior, area praetectalis, dorsal reticular formation and, very sparsely, in the periaqueductal gray. In the lower brainstem, fibers ended in the griseum pontis, medial and lateral parabrachial nuclei, lateral pontine and medullary reticular formation, paramedian and dorsal reticular nuclei, solitary tract nucleus and principal as well as spinal trigeminal nuclei. No terminals were found in the hypoglossal nucleus itself; there were, however, terminals in the immediately bordering reticular formation.

Animals↗

PubMed2002

Activation of JNK by TPA promotes apoptosis via PKC pathway in gastric cancer cells.

AIM: JNK cascade plays an important role in cell proliferation, differentiation and apoptosis. However, the exact function of JNK cascade for apoptosis induction remains largely unknown. In this study, the role of JNK activation stimulated by TPA in the process of apoptosis induction and its signaling transduction pathway in gastric cancer cells were investigated and determined. METHODS: Expressions of mRNA and protein were detected by Northern blot and Western blot. Transcription activity was measured by transient transfection and CAT assay. Apoptotic cells were displayed through staining the nucleus with DAPI and were observed under fluorescence microscope. The apoptotic index was determined by counting 1000 cells randomly. RESULTS: JNK protein was stimulated rapidly by TPA, and reached its highest peak within 3 hr, then decreased in a time-dependent manner, but the expression level of JNK protein induced by TPA was always keeping higher than that in untreated cells. Similar pattern was seen in c-jun mRNA level induced by TPA. TPA significantly activated the transcriptional activity of activator protein-1 with a TPA-dose-dependent manner. Furthermore, activation of JNK was mediated through PKC pathway. Treatment of cells with PKC specific inhibitor, Wortmannin, led to repression of JNK even in the presence of TPA. More importantly, all these effects were associated with induction of apoptosis in gastric cancer cells. TPA inducted apoptosis obviously in gastric cancer cells. The apoptotic cells became smaller and rounded, and their nuclei became condensation and fragmentation with brightly stained chromatin. However, suppression of JNK by PKC specific inhibitor, Wortmannin, resulted in the decrease of apoptosis induced by TPA in a time-dependent manner, apoptotic index dramatically decreased from 32.56 % to 8.71 %. CONCLUSION: TPA stimulates JNK cascade, including up-regulation of JNK protein expression level and c-jun mRNA expression level, and activation of activator protein-1 transcriptional activity. Activation of JNK is mediated through PKC pathway, which has an association with induction of apoptosis by TPA. Thus, activation of JNK via PKC pathway may represent one of important mechanisms for TPA to induce apoptosis in gastric cancer cells.

Apoptosis↗

PubMed2002

[Selected elimination of mouse alloreactive T cells by Fas-FasL passway].

OBJECTIVE: To explore a new method of alleviating graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) through selected elimination of mouse alloreactive T cells (ARTC) by Fas-Fas ligand (FasL) passway. METHODS: The Sca-1(+) early hematopoietic cells (EHCs) were isolated from BALB/c mouse (H-2(d)) bone marrow mononuclear cells (BMMC) by using a high gradient magnetic cell sorting system (MACS), then transferred with exogenous mouse FasL (mFasL) gene by retroviral gene transfecting technique. Afterward the transduced EHCs were expanded in vitro for one week followed by coculture with the spleen cells from BAC mouse (H-2(d) x b) as one-way mixed lymphocyte culture (OWMLC) for 6 days, then the cytotoxicity of treated BAC mouse spleen cells against Na(2)(51)CrO(4) labelling spleen cells from BALB/c mouse was observed. RESULTS: The Sca-1(+) EHCs were successfully isolated by MACS, with a purity of (89.0 +/- 6.1)%. After transferred with exogenous mFasL gene and expanded for one week, the transferred EHCs in the 6 day OWMLC with the spleen cells from BAC mouse at a ratio of five to one resulted in an obvious inhibition of the BAC mouse spleen cells cytotoxicity against the BALB/c mouse spleen cell at different effector/target ratios as compared to the control group (P < 0.01). CONCLUSION: The higher exogenous mFasL-expressing mouse EHCs can deplete ARTC against their own major histocompatibility complex (MHC) antigens in vitro.

Animals↗

PubMed2002

[Expression of histone-based fusion protein HNHG in E.coli].

Histone H1 contributes to condense nucleosome into super-structure during the transformation of chromatin into chromosome. It is shown in this rep or t that the fusion protein HNHG with the core of C-terminus of histone H1(0) expressed in BL21 (DE3) could also condense the plasmid DNA, just as histones did in nucleus. Under electron microscope, plasmid DNA condensed and supercoiled after t he addition of HNHG, in contrast to plasmid DNA control. This specific ability of the fusion protein HNHG of binding and condensing plasmids could be utilized to construct novel exogenous gene delivery systems. HNHG would be a promising candidate for gene delivery.

DNA, Superhelical↗

PubMed2002

[Effect of Epstein-Barr virus latent membrane protein 1 (LMP1) on apoptosis of nasopharyngeal carcinoma cell line CNE1].

BACKGROUND & OBJECTIVE: It was proved that Epstein-Brarr virus (EBV) latent membrane protein 1 (EBV-LMP1) has transformation function which plays an important role in the genesis and development of nasopharyngeal carcinoma (NPC) and this function may be associated with apoptosis. This study was designed to investigate the effect of EBV-LMP1 on apoptosis of NPC CNE1 cell line and to explore the possible mechanism of the function of EBV-LMP1 in the genesis and development of NPC. METHODS: The authors transfected LMP1 eukaryotic expression plasmid carried with the green fluorescent protein (GFP) reporter gene into CNE1 cell line by electroporation. The expression of GFP was detected by fluorescent microscope; the expression of aimed gene LMP1 was detected by immunohistochemistry and Western blot; the effect of LMP1 on apoptosis of CNE1 cells which were treated either with dexamethasone sodium phosphate or serum starvation was investigated by flow cytometry analysis, fluorescence staining, and DNA fragmentation analysis. RESULTS: The green fluorescence could be detected in CNE1G cells transfected by control plasmid PAT-GFP and in CNE1GL cells transfected by plasmid PAT-GFP-LMP1, while there was no GFP expression in CNE1 cells untransfected by any plasmid. LMP1 could be detected in CNE1CL cells, but not in CNE1 and CNE1C cells. Apoptosis could be observed in three groups cells which were treated either with dexamethasone sodium phosphate or serum starvation, and the apoptosis index (AI) of CNE1CL cells was higher than that in CNE1 and CNE1G cells (P < 0.05). There were no apoptosis occurring in three group cells when cultured in regular medium. CONCLUSIONS: The LMP1 gene was transfected successfully into CNE1 cells which were stably expressing LMP1. LMP1 could increase apoptosis occurring of CNE1 cells in the process of inducing apoptosis.

Apoptosis↗

PubMed2002

[Nausea disintegrating buccal tablet in the prevention of gastrointestinal reaction induced by anticancer drugs].

OBJECTIVE: To evaluate the efficacy and safety of nausea oral, disintegrating buccal tablet (DBT) in the prevention of gastrointestinal reaction induced by anticancer drugs (cisplatin DDP 30 - 50 mg/m(2) or adramycin ADM >/= 40 mg/m(2)), as compared with those of kytril tablets. METHODS: A multicenter, open and randomized self-crossover control trial was carried out with all the eligible patients randomized into AB or BA group. Patients in AB group were given nausea 0.1 mg as buccal tablet one hour before chemotherapy in the first cycle and kytril tablet 2 mg in the second cycle, those in BA group were given these drugs in the reverse order. RESULTS: Seventy-three patients were allotted to this study, including 44 patients in DDP-arm and 29 in ADM-arm. Sixty-two patients were evaluable for response and 70 patients for safety. Nausea DBT was as effective as kytril tablet in the control of anorexia, nausea and vomiting during the first 24 hours after chemotherapy, with response rates of 74.2%, 77.4%, 83.9% in nausea DBT and 74.2%, 71.0%, 88.7% DBT in kytril tablets. A high efficacy in the control of vommitting induced by cisplatin was observed in both nausea DBT and kytril tablets. The complete control rates and overall control rates were 83.3%, 91.7% in nausea DBT and 86.1%, 97.2% in kytril tablets, respectively. The side effects of nausea DBT were head heaviness, dry mouth and somnolence, which were mild and comparable with kytril in their frequencies. CONCLUSION: Nausea disintegrating buccal tablet is able to effectively prevent gastrointestinal reaction induced by anticancer drugs, with efficacy and side effects similar to kytril tablets. Nausea DB tablet, an intraoral disintegrator, is very convenient for patients who can not swallow tablets for various reasons.

Adolescent↗

PubMed2002

[Apoptosis of Fas(+) Yac-1 cells induced with Fas ligand-transfected COS-7 cells].

The possibility of immunotherapy for lymphoma by single FasL-Fas way was investigated. After pBillneo-mFasL was transformed into competent E. coli DH5alpha and amplified, the plasmid DNA was prepared and purified from the DH5alpha. To determine the primary structure and inserting direction of mFasL cDNA gene in pBillneo-mFasL, the plasmid DNA was cleaved by restriction enzyme, and the mFasL cDNA of pBillneo-mFasL was amplified by polymerase chain reaction (PCR), the DNA sequence of the PCR product was analysed by automatic DNA sequencing. After pBillneo-mFasL was transfected into COS-7 cells by liposome, the COS-7 cells were selected with G418 selective medium, and the expressing levels of mFasL cDNA on the COS-7 cell membrane was assayed by Western Blot. After the COS-7 cells higher expressing mFasL protein and mouse lymphoma cell line Yac-1 expressing Fas were cocultured for 5 hours, the suspending Yac-1 cells were collected and labeled by annexin V/PI kit. The apoptosis rate of the Yac-1 cells was tested by flow cytometry. The EcoRI cleaving products of pBillneo-mF asL included 920 bp and 7227 bp fragments. Its Hind III cleaving products included 1293 bp and 6807 bp fragments. These results showed: (1) the length of DNA sequence containing mFasL cDNA within pBillneo-mFasL is the same as theoretical length; (2) the inserting of mFasL cDNA in pBillneo-mFasL was in positive orientation. The expected 890 bp DNA fragments of mFasL cDNA (from ATG to +36 bp following TAA) emerged in PCR product with pBillneo-mFasL as a template. The sequencing result of the PCR product equaled the known mFasL cDNA sequence in the gene bank. The COS-7 cells transfected by pBillneo-mFasL and selected with G418 culture medium expressed more mFasL membrane protein assayed by Western Blot. After the COS-7 cells were cocultured with Fas(+) Yac-1 cells in different E:T ratios (1:1, 5:1 and 10:1) for 5 hours, the apoptosis rates of Yac-1 cells were (22 +/- 4.8)%, (32.18 +/- 7.8)%, and (51.8 +/- 5.4)%, respectively. These were obviously different from the control group (P < 0.01), in which the COS-7 cell was transfected by pBillneo (not carrying mFasL gene). It was concluded that lymphoma cells highly expressing Fas can be effectively killed through single Fas-FasL way in vitro.

Animals↗

PubMed2002

[Individual susceptibility to hematotoxicity from benzene exposure and the genetic polymorphism of metabolic enzymes].

Benzene is one of wildly used chemicals. Long-term exposure to benzene causes hematotoxicities and further, the development of including anemia, myelodysplastic syndrome (MDS), aplastic anemia, etc., with the leukemia as the worst. People vary greatly in their susceptibility to adverse health outcomes from benzene exposure. The author reviewed the relationship between genetic polymorphism of I metabolic enzymes(CYP2E1, NQO1, MPO) and II metabolic enzymes(GST, PST) involving benzene metabolite and interindividual variation in their genetic susceptibility to hematotoxicity from benzene exposure in this paper.

Air Pollutants, Occupational↗

PubMed2002

[A retrospective study of clinical manifestation and human papilloma virus detection of oral condyloma acuminate in children].

OBJECTIVE: The aim of this study is to study genotype, transmission, clinical and pathological characteristics, and prognosis of oral condyloma acuminate (CA) in children. METHODS: The authors retrospected the clinical characteristics and slices of HE staining of six cases which have been diagnosed as oral CA and, performed inmunohistochemistry (IHC) and in situ hybridization (ISH) analysis to detect the DNA of human papilloma virus in 5 cases. RESULTS: Oral CA often happened in the hard or soft plates of children of two-year-old. Most of them came from the families had been infected by human papilloma virus (HPV). Histological examination demonstrated that koilocytes were common in the upper spinous and corneal layers. HPV was detected in all cases. HPV16/18-E6 antigen was positive in 4 of 5 cases examined. The result of ISH only show one case was HPV6- and HPV11-positive, and the other case was HPV-positive, but HPV could not be detected when recurring. CONCLUSION: The pathogen leading to oral condyloma acuminate (CA) and the transmission way of children may be different from that of adults.

Child, Preschool↗

PubMed2002

[Determination of arsenic in animal liver by atomic fluorescence spectrometry].

An atomic fluorescence spectrometry for the determination of micro arsenic in animal liver was developed with high sensitivity and fine accuracy. Under the selected experimental conditions, there was a linear relationship between the fluorescence intensity and arsenic concentration in the range of 0-160 ng.mL-1 with correlation coefficient of 0.9996. The limit of detection was 0.4 ng.mL-1, and the recovery was 94.2%-98.5%.

Animals↗

PubMed2002

[Study on the role of calcium signal during mature resumption of isolated mouse germinal vesicles in a cell free system].

A cell-free system including HeLa cell lysate of synchronized metaphase or G2-phase and isolated germinal vesicles (GV) from mouse oocytes was used to study the role of calcium and its downstream mediator during mature resumption. The isolated GVs could resume meiotic maturation in the lysate prepared from M phase HeLa cell, which marked by chromatin condensation. And this process was not affected by calcium chelating agent. But calcium in lysate from G2 phase cells was critical to meiotic maturation. Only in mid-G2 phase cell lysate (released from nocodazole for about 20-23h) chromatin condensation could be induced by calcium. Calcium had no effect on the cell lysate prepared from earlier (18-20h) and later (24h) G2 phase cells. Further studies showed that down stream mediator CaM and CaMKII might also involove in this process. Inhibition the function of CaM and CaMKII could block GVBD and first polar body extrusion of DOs cultured in vitro. The target of calcium signal might be MPF because MPF was existed from mid-G2 phase to metaphase and the tyrosine phosphorylation level of Cdc2 subunit was significantly dephosphorylated in M phase. Our results further confirmed that the resumption of meiosis maturation was promoted in a calcium/CaM depended pathway.

Animals↗

PubMed2002

[The insertion/deletion polymorphism of angiotensin I converting enzyme gene and coronary heart disease--discordant sib pair analysis and transmission/disequilibrium test].

To investigate whether the insertion/deletion polymorphism of the human angiotensin I converting enzyme gene increased the risk of coronary heart disease (CHD) in CHD pedigrees,discordant sib pair analysis (DSP) and transmission/disequilibrium test (TDT) were used. Forty-five CHD pedigrees with at least one CHD patient in the first degree relatives of probands were recruited during Oct. 1998 to Feb. 1999, of which parental genotype known, one or both parental genotype missing was 21.2 and 22 respectively. ACE genotype was measured by PCR technique. Conditional Logistic regression was used to analyze the DSP, and TDT-STDT program 1.1 was used for TDT and STDT. Univariable conditional Logistic regression did not find significant difference of the distribution of three different ACE genotypes in the 106 discordant sib pairs obtained from the 45 pedigrees. After adjusting effects of traditional risk factors of CHD, no significant difference of the distribution was found by multiple Logistic regression model. Neither the TDT for 13 nuclear families or STDT (sib transmission/disequilibrium test) for 24 sibships showed significant difference between the transmitted and untransmitted ACE gene D allele distributions. Our results show that the insertion/deletion polymorphism of ACE gene is not associated or linked with CHD in Chinese population.

English Abstract↗

PubMed2001

The Thioredoxin Reductase-deficient E.coli Mutant Enhances Expression into Solution of Recombinant Proteins Containing Cys Residues.

A 3D artificial protein, a salmon calcitonin hexa-polymer, a salmon calcitonin octo-polymer and a human prourokinase, was expressed in the cytoplasma of E.coli GJ980(trxB(-)) mutant. These recombinant proteins containedcysteine residues of different length ranging from 12-22 residues. The mutation was mapped to the gene for thioredoxin reductase(trxB) and was found to eliminate the activity of this enzyme, which was thought to contribute to the sulfhydryl reducing potential of the cytoplasm. Recombinant salmon calcitonin hexapolymer, salmon calcitonin octo-polymer and human prourokinase had more soluble form in cytoplasm of GJ980 mutants than in wild-type strain, while 3D-protein, which has nocysteine residue, still remain in insoluble form. Results indicate the GJ980(trxB(-)) strain allowed the formation of disulphide bonds in the cell cytoplasm which is believed to encourage correct folding and soluble expression of the recombinant proteins.

Journal Article↗

PubMed2000

A Recombinant Monomeric Human Insulin Mutant with Resistance to Trypsin Design, Preparation and Characterization.

By using a gapped duplex DNA method, the four amino acids on the B chain of insulin, i.e. B22Arg, B28Pro, B29Lys and B30Thr, were mutagenized simultaneously into B22Asp, B28Lys, B29Pro and B30Lys, respectively. The recombinant B22Asp B28Lys B29Pro B30Lys human insulin was obtained simply by the treatment with trypsin of the precursor that was expressed in yeast. This human insulin analog had only 6% of receptor binding activity as that of the porcine insulin, but retained 50% of in vivo biological activity, compared with the latter. The self-association ability of the mutant measured through FPLC gel filtration chromatography showed that it was in monomeric state. As a monomeric insulin analog with resistance to the trypsin digestion, this compound may be promising in practical application.

Journal Article↗