Bispecific antibody simultaneously targeting PD1 and HER2 inhibits tumor growth via direct tumor cell killing in combination with PD1/PDL1 blockade and HER2 inhibition.

Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year.

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis.

The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress.

Background: Diallyl disulfide (DADS) is a garlic-derived organosulfur compound. The current study is designed to evaluate the protective effects of DADS against ethanol-induced oxidative stress, and to explore the underlying mechanisms by examining the HO-1/Nrf-2 pathway.

Methods: We investigated whether or not DADS could activate the HO-1 in normal human liver cell LO2, and then evaluated the protective effects of DADS against ethanol-induced damage in LO2 cells and in acute ethanol-intoxicated mice.

Garlic oil suppressed the hematological disorders induced by chemotherapy and radiotherapy in tumor-bearing mice.

Although the anticancer effects of garlic and its products have been demonstrated by a variety of studies; however, few studies were conducted to investigate the effects of garlic on the adverse effects of chemo/radiotherapy. In order to clarify the above question and make a more comprehensive understanding of the anticancer effects of garlic, tumor xenograft mice model was established by subcutaneous injection of H22 tumor cells, and was used for the investigation of effects of garlic oil (GO) on the chemo/radiotherapy. In the chemotherapy test, tumor-bearing mice were treated with cyclophosphamide (CTX) or CTX plus GO (25 or 50 mg/kg bw) for 14 d, while the mice received a single 5 Gy total body radiation or radiation plus GO (25 or 50 mg/kg bw) in radiotherapy test.

PI3K/Akt pathway activation was involved in acute ethanol-induced fatty liver in mice.

Accumulating evidences support the important roles of sterol regulatory element-binding protein-1 (SREBP-1) activation in ethanol-induced fatty liver, but the underlying mechanisms for its activation are not fully understood. Recent studies have demonstrated that phosphatidylinositol 3 kinase (PI3K)/Akt pathway activation could enhance SREBP-1 activity. The current study was designed to investigate the potential roles of PI3K/Akt pathway in acute ethanol-induced fatty liver in mice.

Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats.

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms.

[Effects of 1-bromopropane exposure on cognitive function in rats].

Objective: To study the effects of 1-bromopropane (1-BP) on the functions of learning-memory and the central cholinergic system in rats.

Methods: Forty male Wistar rats were randomly divided into four groups: low 1-BP group (200 mg/kg), middle 1-BP group (400 mg/kg), high 1-BP group (800 mg/kg) and control group, and the exposure time was 7 days. The Morris water maze (MWM) test was applied to evaluate the learning-memory function in rats.

[The effects of tea polyphenols on the injury of fibrinolytic functions induced by high-methionine dietary in rats].

Objective: To study the protective impact of tea polyphenols (TP) on the injury of fibrinolytic functions induced by high-methionine dietary in rats.

Methods: 50 male Wistar rats were divided by stratified based on body weight into 5 groups with 10 in each group: namely control group, model group, low-dose TP group, medium-dose TP group and high-dose TP group. The rats in model group and TP groups were fed with 3% methionine dietary, control group rats with routine diet.

[Effects of tacrolimus (FK506) on heat-shock proteins 70, Bcl-2 and Bax expression in nervous tissue of acrylamide-induced rat].

Objective: To investigate the effects of tacrolimus (FK506) on behavioral function and heat-shock proteins (HSP70) expression in nervous tissues of acrylamide (ACR)-induced rats.

Methods: Totally 40 health Wistar rats were randomly divided into control group, model group, low and high doses of FK506 groups. All four groups were treated five times per week for four weeks.

Ortho effects on the change in electronic absorption spectrum of pyridinium salts of saturated bromohydrocarbon.

The quaterisation process of 1,2-dibromoethane and pyridine is in situ traced by electronic absorption spectrum. Two absorption peaks, induced by mono- and bis-pyridinium salt of 1,2-dibromoethane, appear at 429 nm and 313 nm, respectively. To explain the phenomena, several kinds of alkyl bromides with special structures were selected and compared by experimental measurement and theoretical calculation.

[Effects of garlic oil on n-hexane metabolized to 2, 5-hexanedione in mice serum].

Objective: To investigate the effects of garlic oil (GO) on n-hexane metabolized to 2, 5-hexanedione (2, 5-HD) in mice.

Methods: Adult healthy Kunming-mice were treated with n-hexane and GO. The serum was obtained and extracted with ethyl acetate, and the levels of the serum 2, 5-HD were determined by gas chromatography.

[Dynamic study of neurofilament contents in rat's spinal cord induced by 2, 5-hexanedione].

Objective: To investigate the dynamic changes of neurofilament contents in rat's spinal cord induced by 2, 5-hexanedione (2, 5-HD), and explore the molecular mechanism of n-hexane neuropathy.

Methods: Male Wistar rats were administered at a dosage of 400 mg/kg/day 2, 5-HD for 2, 4 and 8 weeks respectively. HD-induced neurological defects were detected and quantified using gait score, and the relative lev-els of NF-H, NF-M, and NF-L in spinal cords of rats were determined by Western Blotting.

[Study on the skin-core evolvement of carbon fibers as a function of heat treatment temperature by Raman spectroscopy].

The skin-core evolvement of the carbon fibers was studied as a function of heat-treatment temperature though the analysis of Raman spectroscopy of the carbon fibers surface and core. It was found that the change of the Raman spectra of the carbon fibers core was similar to that on the surface with the increase in heat-treatment temperature. At 1600 degrees C, the Rs and Rc values were almost equal, indicating that the degrees of the graphitization of the carbon fibers surface and core were almost uniform.

Diallyl trisulfide (DATS) effectively attenuated oxidative stress-mediated liver injury and hepatic mitochondrial dysfunction in acute ethanol-exposed mice.

The protective effects of diallyl trisulfide (DATS) on acute ethanol-induced liver injury were investigated. Mice were pretreated with DATS (30mg/kgbw) for 7d before being exposed to ethanol (4.8g/kgbw).

[Cloning and expression of the extracellular domain of 4-1BBL].

RT-PCR was used to clone DNA fragment of the extracellular domain of 4-1BBL from human THP-1 cells (human monocyte), and the expression vector pAYZ4-1BBL was constructed by cloning the extracellular domain of 4-1BBL into the expression vector pAYZ. The extracellular domain of 4-1BBL was expressed in E. coli 16C9 and purified by affinity chromatography.

[Effects of methamidophos on microtubule and microfilament proteins in sciatic nerve of hens].

Objective: To investigate the dynamic changes of alpha-tubulin, beta-tubulin and beta-actin in sciatic nerve of hen with organophosphorus ester-induced delayed neuropathy (OPIDN).

Methods: OPIDN was induced in 10-month-old Roman hens by daily subcutaneous administration of 30 mg/kg methamidophos for 15 days. Hens were sacrificed 2, 10, and 23 days respectively after manifesting neuropathy.

[Construction and expression of single chain Fv gene against domain II of human VEGF receptor II].

The genes encoding for the light and heavy chain variable regions (V(H) and V(L)) has been cloned by RT-PCR from a murine hybridoma that produced monoclonal antibody (mAb) Ycom1D3, which was against domain III of human vascular endothelial growth factor receptor II (KDRIII) and were then connected to each other by a short peptide linker containing 15 amino acids (Gly4Ser)3 using splice-overlap extensive PCR. The recombinant Ycom1D3-ScFv gene was cloned into the expression vector pAYZ and induced to express in E. coli 16C9.

[Construction and expression of anti-CD3/ anti-Pgp Diabody].

The use of tumor antigen specific antibodies for the delivery of therapeutic agents offers the possibility of targeting therapy with reduced toxicity to normal tissues compared to conventional treatments. However, several factors restrict the use of anti-PGP monoclonal antibodies(Mabs). First, Pgp is expressed in normal tissues, particularly in epithelial and endothelial cells of the gastrointestinal tract, liver, kidney, blood brain barrier, choroids plexus and other organs.

[One amino acid mutation in an anti-CD20 antibody fragment that affects the yield bacterial secretion and the affinity].

Monoclonal antibodies (mAb) directed against CD20, either unmodified or in radiolabeled forms, have been successfully exploited in clinic as effective therapeutic agents in the management of non-Hodgkin's B-cell lymphoma. The antibody fragment is a potential agent in image and therapy of tumor. To further improve the soluble expression of anti-CD20 antibody Fab' fragment, PCR was used to mutate the anti-CD20 VL and VH genes and its biological activity was identified.

[Effect of monoclonal antibody against extracellular domain III of vascular endothelial growth factor receptor KDR on proliferation of vascular endothelial cells].

Objective: To prepare a neutralizing monoclonal antibody (McAb) against vascular endothelial growth factor receptor KDR and study its biological activity.

Methods: Extracellular immunoglobulin (Ig)-like domain III of KDR (KDR III) was expressed in E. coli and purified by affinity chromatograph.

[Alterations of neurofilament proteins in sciatic nerve of hens induced the delayed neurotoxicity by methamidophos].

Objective: To investigate the dynamic alterations of neurofilament subunits (NF) in sciatic nerve of hens with organophosphorus ester induced the delayed neurotoxicity or neuropathy (OPIDN).

Methods: Hens with OPIDN were produced by giving 30 mg/kg methamidophos subcutaneously to the 10-month-old Roman hens daily for 15 days, and sacrificed after manifesting neurotoxic clinical signs on the 2nd, 10th, and 23rd day respectively. The sciatic nerves were dissected, homogenized and centrifuged.

[Prokaryotic expression and characterization of an anti-KDR single chain antibody].

Aim: To construct and express a single chain antibody (scFv) against human vascular endothelial growth factor (VEGF) receptor KDR and characterize its biological activity.

Methods: The restriction enzyme sites were added to the previously cloned V(H) and V(L) genes of mAb Ycom1D3 against KDR by PCR. The anti-KDR scFv gene was constructed by the splicing overlap extensive (SOE) PCR and then inserted into fusion expression vector pAYZH.

Production of neutralizing monoclonal antibody against human vascular endothelial growth factor receptor II.

Aim: To prepare neutralizing monoclonal antibody (mAb) against extracellular immunoglobulin (Ig)-like domain III of vascular endothelial growth factor receptor KDR and study its biological activity.

Methods: Soluble KDR Ig domain III (KDR-III) fusion protein was expressed in E Coli and purified from the bacterial periplasmic extracts via an affinity chromatography. Monoclonal antibodies against KDR-III were prepared by hybridoma technique.

Tri-ortho-cresyl phosphate (TOCP) decreases the levels of cytoskeletal proteins in hen sciatic nerve.

Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester. It is capable of producing organophosphorus ester induced delayed neurotoxicity (OPIDN) in human being and sensitive animals, which is characterized by ataxia that progresses to paralysis after 1-3 weeks following exposure to some organophosphorus ester. In present study, 18 adult hens were divided randomly into three groups, i.

[Apoptosis of human B cell lymphoma Raji cells induced by monovalent anti-CD20 antibody].

Background & Objective: The anti-CD20 antibodies and fragments have been applied for treatment of non-Hodgkin's lymphomas (NHL) in clinic. The new anti-CD20 antibodies and their fragments (unmodified or radiolabeled) yet have been exploited for those patients with incomplete response to rituximab. The chimeric antibody fragments Fab and F(ab) '(2) derived from HI(47)(a mouse anti-CD20 antibody) have been constructed.