T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models.

Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential.

Interaction of Wnt pathway related variants with type 2 diabetes in a Chinese Han population.

Aims. Epistasis from gene set based on the function-related genes may confer to the susceptibility of type 2 diabetes (T2D). The Wnt pathway has been reported to play an important role in the pathogenesis of T2D.

Expression profiles of miRNAs in Gossypium raimondii.

miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA molecules with 20-24 nucleotides (nt) in length that function as post-transcriptional modulators of gene expression in eukaryotic cells. Functional studies have demonstrated that plant miRNAs are involved in the regulation of a wide range of plant developmental processes. To date, however, no research has been carried out to study the expression profiles of miRNAs in Gossypium raimondii, a model cotton species.

Thyroid hormone attenuates vascular calcification induced by vitamin D3 plus nicotine in rats.

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) play critical roles in bone remodeling. However, the role and mechanism of THs in vascular calcification (VC) have been unclear. To explore the pathophysiological roles of T3 on VC, we investigated the changes in plasma and aortas of THs concentrations and the effect of T3 on rat VC induced by vitamin D3 plus nicotine (VDN).

Cinchona alkaloids from Cinchona succirubra and Cinchona ledgeriana.

Seven new cinchona alkaloids, cinchonanines A-G (1-7), and 29 known alkaloids were isolated from the barks of Cinchona surrirubra and C. ledgeriana collected from Yunnan Province in China. The new structures were elucidated by extensive spectroscopic analysis.

Melosuavines A-H, cytotoxic bisindole alkaloid derivatives from Melodinus suaveolens.

Eight new bisindole alkaloids, melosuavines A-C (1-3), having an aspidosperma-scandine linkage, melosuavines D-F (4-6), possessing an aspidosperma-aspidosperma skeleton, and melosuavines G and H (7 and 8) of the aspidosperma-venalatonine type, tenuicausine (9), and melodinine J (10) were isolated from the twigs and leaves of Melodinus suaveolens. The structures of 1-8 were elucidated by extensive spectroscopic methods, and compounds 9 and 10 were identified by comparison with data in the literature. The relative configuration 9 was determined from the ROESY spectrum, and some NMR signals were reassigned.

Gardovatine, a novel Strychnos-Strychnos bisindole alkaloid with cytotoxicity from Gardneria oveta.

Gardovatine (1), the first Strychnos-Strychnos alkaloid with a C3/C7 cleaved backbone, was isolated from twigs and leaves of Gardneria ovate, together with an analogue divarine (2). The structure was established by extensive spectroscopic methods. Both compounds showed potential cytotoxicities against five human cancer cell lines.

Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway.

We previously reported that endoplasmic reticulum (ER) stress-mediated apoptosis participated in vascular calcification. Importantly, a novel paracrine/autocrine peptide intermedin1-53 (IMD1-53) in the vasculature inhibited vascular calcification in rats. But the mechanisms needed to be fully elucidated.

Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification.

Our previous work reported that endoplasmic reticulum stress (ERS)-mediated apoptosis was activated during vascular calcification (VC). Activating transcription factor 4 (ATF4) is a critical transcription factor in osteoblastogenesis and ERS-induced apoptosis. However, whether ATF4 is involved in ERS-mediated apoptosis contributing to VC remains unclear.

Transforming growth factor-β1 gene mutations and phenotypes in pediatric patients with Camurati‑Engelmann disease.

The aim of the present study was to investigate the clinical characteristics and major causative gene in pediatric patients with Camurati‑Engelmann disease (CED). Biochemical and radiographic examinations, bone scintigraphy and genetic analyses were performed in two affected males and their parents. The two patients experienced waddling gait, muscular weakness and growth developmental delay.

The A242T mutation in the low-density lipoprotein receptor-related protein 5 gene in one Chinese family with osteosclerosis.

Objective: Osteosclerosis (OMIM: 144750) is a type of autosomal dominant bone disease caused by a mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The case of a Chinese family with two affected individuals is reported in the present study in order to investigate the clinical characteristics and virulence genes of this sclerosing bone disorder.

Methods: Biochemical and radiographic examinations and bone mineral density (BMD) and genetic analyses were performed in two patients and eight other family members.

Angiotensin-(1-7) inhibits vascular calcification in rats.

Angiotensin-(1-7) [Ang-(1-7)] is a new bioactive heptapeptide in the renin-angiotensin-aldosterone system (RAAS) with potent protective effects in cardiovascular diseases, opposing many actions of angiotensin II (Ang II) mediated by Ang II type 1 (AT1) receptor. It is produced mainly by the activity of angiotensin-converting enzyme 2 (ACE2) and acts through the Mas receptor. However, the role of Ang-(1-7) in vascular calcification (VC) is still unclear.

[The relationship between hyperuricaemia and clinic pathology of IgA nephropathy].

Objective: To analyze the correlation between the level of serum uric acid and the clinical and pathological features of IgA nephropathy.

Methods: Totally 148 patients diagnosed as IgA nephropathy by renal biopsy in our hospital from January 2007 to December 2010 were divided into hyperuricaemic group (41 cases) and non-hyperuricaemic group (107 cases) according to the level of serum uric acid. The clinical parameters and renal pathology grade were compared.

Adrenomedullin protects against fructose-induced insulin resistance and myocardial hypertrophy in rats.

Adrenomedullin (ADM) has been recognized as a multipotent multifunctional peptide. To explore the pathophysiological roles of ADM in insulin resistance (IR), we studied the changes in ADM mRNA level in the myocardium and vessels and the effect of ADM supplementation on rats with IR induced by fructose feeding. Rats were fed 4% fructose in drinking water for 8 weeks, and ADM was administered subcutaneously in pure water through an Alzet Mini-osmotic Pump at 300 ng/kg/h for the last 4 weeks.

Deep sequencing identifies novel and conserved microRNAs in peanuts (Arachis hypogaea L.).

Background: MicroRNAs (miRNAs) are a new class of small, endogenous RNAs that play a regulatory role in the cell by negatively affecting gene expression at the post-transcriptional level. miRNAs have been shown to control numerous genes involved in various biological and metabolic processes. There have been extensive studies on discovering miRNAs and analyzing their functions in model species, such as Arabidopsis and rice.

Genome-wide computational identification of microRNAs and their targets in the deep-branching eukaryote Giardia lamblia.

Using a combined computational program, we identified 50 potential microRNAs (miRNAs) in Giardia lamblia, one of the most primitive unicellular eukaryotes. These miRNAs are unique to G. lamblia and no homologues have been found in other organisms; miRNAs, currently known in other species, were not found in G.

Effect and mechanism of nociceptin/orphanin FQ reversing multi-drug resistance in K562/ADM cell.

Objective: To investigate the effect and mechanism of nociceptin/orphanin FQ (OFQ) reversing multi-drug resistance of K562/ADM cells in vitro.

Methods: MTT assay, Wright staining, flow cytometry, transmission electron microscope and gel electrophoresis were used to evaluate the effect and mechanism of OFQ in reversing multi-drug resistance of K562/ADM cells.

Results: OFQ could time-dependently reverse the ADM resistance of K562/ADM cell.

Preclinical pharmacokinetics of a HepDirect prodrug of a novel phosphonate-containing thyroid hormone receptor agonist.

The prodrug [(2R,4S)-4-(3-chlorophenyl)-2-[(3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxy)methyl]-2-oxido-[1,3,2]-dioxaphosphonane (MB07811)] of a novel phosphonate-containing thyroid hormone receptor agonist [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)phenoxylmethylphosphonic acid (MB07344)] is the first application of the HepDirect liver-targeting approach to a non-nucleotide agent. The disposition of MB07811 was characterized in rat, dog, and monkey to assess its liver specificity, which is essential in limiting the extrahepatic side effects associated with this class of lipid-lowering agents. MB07811 was converted to MB07344 in liver microsomes from all species tested (CL(int) 1.

Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index.

Despite efforts spanning four decades, the therapeutic potential of thyroid hormone receptor (TR) agonists as lipid-lowering and anti-obesity agents remains largely unexplored in humans because of dose-limiting cardiac effects and effects on the thyroid hormone axis (THA), muscle metabolism, and bone turnover. TR agonists selective for the TRbeta isoform exhibit modest cardiac sparing in rodents and primates but are unable to lower lipids without inducing TRbeta-mediated suppression of the THA. Herein, we describe a cytochrome P450-activated prodrug of a phosphonate-containing TR agonist that exhibits increased TR activation in the liver relative to extrahepatic tissues and an improved therapeutic index.

[Apoptosis of K562 cells induced by nociceptin/orphanin FQ].

The study was to investigate the proliferation and apoptosis effect of nociceptin/orphanin FQ (OFQ) on 562 cells in vitro. Inhibition of K562 cells proliferation was measured by MTT assay. Morphological assessment of apoptosis was performed with Wright staining and transmission electron microscope.

Ethanol reduces p38 kinase activation and cyclin D1 protein expression after partial hepatectomy in rats.

Background/aims: Chronic ethanol consumption inhibits liver regeneration. We examined the effects of chronic ethanol consumption on two mitogen-activated protein kinases in relation to induction of cell cycle proteins after partial hepatectomy (PH).

Methods: Male Wistar rats were ethanol-fed (EF) or pair-fed (PF) for 16 weeks before PH.