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Biological effects of multimetal (Ni, Cd, Pb, Cu, Cr, Zn) mixture in rainbow trout Oncorhynchus mykiss: Laboratory exposure and recovery study.

Ecotoxicol Environ Saf 2021 Apr 7;216:112202. Epub 2021 Apr 7.

Nature Research Centre, Laboratory of Geoenvironmental Research, Akademijos St. 2, LT-08412 Vilnius, Lithuania; Vilnius University, Faculty of Chemistry and Geosciences, Naugarduko St. 24, LT-03225 Vilnius, Lithuania.

The present study tested the biological consequences of exposure to a multimetal mixture as a multiple chemical stressor on Oncorhynchus mykiss at molecular, cellular, physiological and whole-organism levels and on biomarker responses of this fish during the depuration period. To represent environmentally relevant multiple chemical stressors, in our study, we used the mixture of Zn, Cu, Ni, Cr, Pb and Cd at the concentrations corresponding to Maximum-Permissible-Concentrations (MPCs) acceptable for the EU inland waters. This study was undertaken with a view to elucidate if changes in the MPC of the test mixture components (Ni, Pb, Cd) could cause significantly different biomarker responses in O. Read More

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Effects of dim artificial light at night on locomotor activity, cardiovascular physiology, and circadian clock genes in a diurnal songbird.

Environ Pollut 2021 Mar 31;282:117036. Epub 2021 Mar 31.

Department of Biology, University of Nevada, Reno, Reno, NV, USA.

Artificial light is transforming the nighttime environment and quickly becoming one of the most pervasive pollutants on earth. Across taxa, light entrains endogenous circadian clocks that function to synchronize behavioral and physiological rhythms with natural photoperiod. Artificial light at night (ALAN) disrupts these photoperiodic cues and has consequences for humans and wildlife including sleep disruption, physiological stress and increased risk of cardiovascular disease. Read More

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MiR-105 enhances osteogenic differentiation of hADSCs via the targeted regulation of SOX9.

Tissue Cell 2021 Apr 2;72:101540. Epub 2021 Apr 2.

Department of Endocrinology, Qinghai University Affiliated Hospital, Xining, Qinghai, China. Electronic address:

Objective: To investigate whether miR-105 can regulate the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) by targeting SOX9.

Methods: The hADSCs were grouped for subsequent transfection and induction of osteogenic differentiation as follows: control, miR-NC, miR-105 mimics, miR-105 inhibitors, SOX9, SOX9 siRNA, miR-105 mimics + SOX9 and miR-105 inhibitors + SOX9 siRNA groups. Next, hADSCs were stained for alkaline phosphatase (ALP), and Alizarin Red S staining (ARS) was performed. Read More

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Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.

Neurotoxicol Teratol 2021 Apr 7:106981. Epub 2021 Apr 7.

Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Emamectin Benzoate (EMB) is an avermectin insecticide widely used in agriculture and veterinary medicine. Hesperidin (HSP) is a flavanone glycoside predominantly found in citrus fruits and has various beneficial health effects. The current research was conducted to study the neurobehavioral toxic effects of EMB in rats and also to evaluate the protective effect of HSP against these toxic effects. Read More

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Effects of high fat diets and supplemental tart cherry and fish oil on obesity and type 2 diabetes in male and female C57BL/6J and TALLYHO/Jng mice.

J Nutr Biochem 2021 Apr 7:108644. Epub 2021 Apr 7.

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA. Electronic address:

Obesogenic and diabetogenic high fat (HF) diets can influence genetic factors in disease development with sexual dimorphic responses. We investigated potential protective effects of tart cherry (TC), fish oil (FO) and TC+FO supplementation in TALLYHO/Jng (TH) and C57BL/6J (B6) mice fed HF diets. Male and female TH and B6 mice were weaned onto five different diets; low fat (LF), HF, and HF supplemented with TC, FO, or TC+FO and maintained. Read More

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MiR-3663-3p participates in the anti-hepatocellular carcinoma proliferation activity of baicalein by targeting SH3GL1 and negatively regulating EGFR/ERK/NF-κB signaling.

Toxicol Appl Pharmacol 2021 Apr 7:115522. Epub 2021 Apr 7.

National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710004, China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Xi'an, Shaanxi 710004, China; Center for Tumor and Immunology, the Precision Medical Institute, the Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address:

Baicalein is a purified flavonoid that exhibits anticancer effects in hepatocellular carcinoma (HCC). However, its underlying molecular mechanisms remain largely unclear. In this study, we found that baicalein inhibited HCC cell growth, induced apoptosis, and blocked cell cycle arrest at the S phase in vitro, as well as reduced HCC tumor volume and weight in vivo. Read More

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The daily gene transcription cycle in mouse retina.

Exp Eye Res 2021 Apr 7:108565. Epub 2021 Apr 7.

Aier School of Ophthalmology, Central South University, Changsha, China; Aier Eye Institute, Changsha, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. Electronic address:

Many physiological retinal processes, such as outer segment disk shedding and visual sensitivity, exhibit a daily rhythm. However, the detailed transcriptome dynamics and related biological processes of the retina are not fully understood. Retinal tissues were collected from C57BL/6J male mice housed in a 12h light/12h dark (LD) cycle for 4 weeks, at Zeitgeber time (ZT) 0, 4, 8, 12, 16, and 20. Read More

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Novel positive allosteric modulator of protease-activated receptor 1 promotes skin wound healing in hairless mice.

Br J Pharmacol 2021 Apr 10. Epub 2021 Apr 10.

College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, 21983, Korea.

Background And Purpose: Protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor expressed in several skin cell types, including keratinocyte and dermal fibroblast. PAR1 activation plays a crucial role in the process of skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated its effect on skin wound healing. Read More

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Circular RNA circ-ARFIP2 regulates proliferation, migration and invasion in human vascular smooth muscle cells via miR-338-3p-dependent modulation of KDR.

Metab Brain Dis 2021 Apr 10. Epub 2021 Apr 10.

Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.106 Zhongshan Second Road, Guangzhou, 510000, Guangdong, China.

Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of intracranial aneurysm (IA). Circular RNAs (circRNAs) have been implicated in the pathogenesis of IA by reducing microRNA (miRNA) activity. In this paper, we investigated the precise roles of circRNA ADP ribosylation factor interacting protein 2 (circ-ARFIP2, circ_0021001) in VSMC dysfunction. Read More

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RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation.

Cancer Immunol Immunother 2021 Apr 10. Epub 2021 Apr 10.

Department of Urology, First Affiliated Hospital, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan Province, People's Republic of China.

Rb1-inducible coiled-coil 1 (RB1CC1) has been demonstrated to function as an inhibitor of proline-rich/Ca-activated tyrosine kinase 2 (PYK2) by binding to the kinase domain of PYK2, which promotes the proliferation, invasion, and migration of renal cell carcinoma (RCC) cells. Additionally, in breast cancer, PYK2 positively regulates the expression of transcriptional co-activator with PDZ-binding motif (TAZ) which in turn can enhance PDL1 levels in breast and lung cancer cells. The current study was performed to decipher the impact of RB1CC1 in the progression of RCC via regulation of the PYK2/TAZ/PDL1 signaling axis. Read More

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A single stiffened nucleus alters cell dynamics and coherence in a monolayer.

Cytoskeleton (Hoboken) 2021 Apr 9. Epub 2021 Apr 9.

Molecular Biophysics and Structural Biology, University of Pittsburgh and Carnegie Mellon University.

Force transmission throughout a monolayer is the result of complex interactions between cells. Monolayer adaptation to force imbalances such as singular stiffened cells provides insight into the initiation of disease and fibrosis. Here, NRK-52E cells transfected with ∆50LA, which significantly stiffens the nucleus. Read More

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Ethylmalonic acid impairs bioenergetics by disturbing succinate and glutamate oxidation and induces mitochondrial permeability transition pore opening in rat cerebellum.

J Neurochem 2021 Apr 10. Epub 2021 Apr 10.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.

Tissue accumulation and high urinary excretion of ethylmalonic acid (EMA) are found in ethylmalonic encephalopathy (EE), an inherited disorder associated with cerebral and cerebellar atrophy whose pathogenesis is poorly established. The in vitro and in vivo effects of EMA on bioenergetics and redox homeostasis were investigated in rat cerebellum. For the in vitro studies cerebellum preparations were exposed to EMA, whereas intracerebellar injection of EMA was used for the in vivo evaluation. Read More

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Dosimetric evaluation of receptor-heterogeneity on the therapeutic efficacy of peptide receptor radionuclide therapy: correlation with DNA damage induction and survival.

J Nucl Med 2021 Apr 9. Epub 2021 Apr 9.

Erasmus MC, Netherlands.

To build a refined dosimetry model for [Lu]Lu-DOTA-[Tyr]octreotate (Lu-DOTATATE) experiments enabling the correlation of absorbed dose with double strand breaks (DSBs) induction and cell death. Somatostatin receptor type-2 (SSTR) expression of NCI-H69 xenografted mice, injected with Lu-DOTATATE, was imaged at 0, 2, 5, 11 days. This was used as input to reconstruct realistic 3 dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells. Read More

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Transcriptomic studies of systemic lupus erythematosus.

Inflamm Regen 2021 Apr 9;41(1):11. Epub 2021 Apr 9.

Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Read More

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Selenium source and level on performance, selenium retention and biochemical responses of young broiler chicks.

BMC Vet Res 2021 Apr 9;17(1):151. Epub 2021 Apr 9.

Department of Animal Science, Federal University of Viçosa, Viçosa, 36570900, Brazil.

Background: Selenium (Se) has been recognized as an essential micronutrient for nearly all forms of life. In recent decades, broiler responses to dietary Se supplemental levels and sources have received considerable attention. On environmental grounds, organic trace mineral utilization in practical broiler feeds has been defended due to its higher bioavailability. Read More

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Heteromerization of Dopaminergic Receptors in the Brain: Pharmacological Implications.

Desye Misganaw

Pharmacol Res 2021 Apr 6:105600. Epub 2021 Apr 6.

Pharmacology and Toxicology unit, Department of Pharmacy, College of Medicine and Health Science, Wollo University, P.O. Box 1145, Dessie, Ethiopia.

Dopamine exerts its physiological effects through two subtypes of receptors, i.e. the receptors of the D family (D and D) and the D family (D, D3R, and D), which differ in their pattern of distribution, affinity, and signaling. Read More

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The K7 modulator, retigabine, is an efficacious antiseizure drug for delayed treatment of organophosphate-induced status epilepticus.

Neuroscience 2021 Apr 6. Epub 2021 Apr 6.

United States Army Medical Research Institute of Chemical Defense, Medical Toxicology Research Division, Neuroscience Department, 2900 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010, USA.

Benzodiazepines are the primary treatment option for organophosphate (OP)-induced status epilepticus (SE), but these antiseizure drugs (ASDs) lose efficacy as treatment is delayed. In the event of a mass civilian or military exposure, significant treatment delays are likely. New ASDs that combat benzodiazepine-resistant, OP-induced SE are critically needed, particularly if they can be efficacious after a long treatment delay. Read More

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Thrombotic Microangiopathy Associated With Macrophage Activation Syndrome: A Multinational Study of 23 Patients.

J Pediatr 2021 Apr 6. Epub 2021 Apr 6.

IRCCS Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy; Sechenov First Moscow State Medical University, Moscow, Russian Federation.

Objective: To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA).

Study Design: International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. Read More

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Effects of aging on proteasomal-ubiquitin system, oxidative stress balance and calcium homeostasis in middle-aged female rat colon.

Physiol Int 2021 Apr 8. Epub 2021 Apr 8.

1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.

Aging is a multifactorial process, which is considered as a decline over time. It is increasingly clear that there is a gender difference in aging and in the prevalence of age-related diseases as well. We aimed to examine the effects of the aging process in the colonic tissue of female Wistar rats aged 10 weeks (young) and 13 months (middle-aged) at an early stage, according to three main symptoms associated with aging: a decrease in the efficacy of the proteasome and muscle function and an increase in oxidative stress. Read More

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Long-Acting Lipoglycopeptides for the Treatment of Bone and Joint Infections.

Surg Infect (Larchmt) 2021 Apr 9. Epub 2021 Apr 9.

Michigan State University College of Human Medicine, East Lansing, Michigan, USA.

The long-acting lipoglycopeptides dalbavancin and oritavancin possess excellent microbiologic activity against gram-positive bacteria and provide prolonged tissue exposure at sites of infection. Moreover, these antibiotics are well tolerated and do not require therapeutic drug monitoring. Pharmacokinetic/pharmacodynamic experiments ascertained that one to two doses of these long-acting agents can provide an extended period (≥6 weeks) of antimicrobial therapy. Read More

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First report of bacterial leaf spot disease on sunflower () caused by in South Korea.

Plant Dis 2021 Apr 9. Epub 2021 Apr 9.

Chungnam National University, 26715, Department of Applied Biology, Daejeon, N/A, Korea (the Republic of);

In September 2019, bacterial leaf spot symptoms were observed on sunflowers in an experimental field in Eumseong, South Korea. The leaves of infected plants initially showed irregular brown spots surrounded by haloes; as the disease progressed, the spots became enlarged and darkened (eXtra Fig. 1a). Read More

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Cell signaling in cutaneous T-cell lymphoma microenvironment: promising targets for molecular-specific treatment.

Int J Dermatol 2021 Apr 9. Epub 2021 Apr 9.

Instituto de Biología, Universidad de Antioquia, Medellin, Colombia.

Cutaneous T-cell lymphomas (CTCL) result from the infiltration and proliferation of a population of T cells in the skin, inducing changes in the activity of both T cells and surrounding skin cells. In the CTCL microenvironment, cell interactions mediated by cell signaling pathways are altered. Defining changes in cell signaling enables to understand T-cell deregulations in the CTCL microenvironment and thus the progression of the disease. Read More

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Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective.

Curr Heart Fail Rep 2021 Apr 9. Epub 2021 Apr 9.

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Purpose Of Review: (Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30-50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. Read More

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Pharmacokinetics, safety, activity, and biomarker analysis of palbociclib plus letrozole as first-line treatment for ER+/HER2- advanced breast cancer in Chinese women.

Cancer Chemother Pharmacol 2021 Apr 9. Epub 2021 Apr 9.

Pfizer Inc, San Diego, CA, USA.

Purpose: This phase 1, open-label, single-arm clinical trial evaluated pharmacokinetics, safety, and biomarker activity of palbociclib-letrozole as first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) in postmenopausal Chinese women to support palbociclib approval in China.

Methods: Patients received palbociclib 125 mg once daily (3/1 schedule) plus letrozole 2.5 mg once daily. Read More

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Probiotic Lactobacillus kefiri prevents endotoxin-induced preterm birth and stillbirth in mice.

Reproduction 2021 Apr 1. Epub 2021 Apr 1.

F Jensen, Immunology of Pregnancy Laboratory, CEFYBO, BUENOS AIRES, Argentina.

Preterm birth (PTB), defined as birth occurring before 37 weeks of pregnancy, affects 5-18% of pregnancies and is the leading cause of neonatal morbidity and mortality worldwide. Although PTB is considered a syndrome, infection-induced inflammation accounts up to 50% of all cases. Despite the effort to reduce the incidence of PTB, it continues rising worldwide and current approaches for preventing or treating PTB are largely unsatisfactory. Read More

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[Serpins as important protective factors in the pathogenesis of acute lung injury/acute respiratory distress syndrome].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):368-372

Department of Abdominal Emergency Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common respiratory disease in clinic, and with a pathological manifestation of pulmonary edema, decreased pulmonary compliance as well as pulmonary epithelial/endothelial cells injury. At present, it was suggested that systemic inflammatory response syndrome (SIRS) caused by various causes which play an important role in the occurrence and development of ALI/ARDS. Widely activated neutrophils can migrate to lung tissue and release plenty of proteases in the procedure of SIRS, including neutrophil serine proteases (NSPs), lysozyme, myeloperoxidase and collagenase, which can induce severe lung injury. Read More

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[Relationship between neutrophil phenotypic and functional heterogeneity and diseases].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):360-363

Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin 300100, China. Corresponding author: Wang Ximo, Email:

Neutrophils are the most abundant circulating leukocyte type in humans and comprise the host's first line of cellular defense against foreign pathogens invasion. On the other hand, neutrophils are the main mediators of tissue damage induced by acute and chronic inflammation. They were once considered to be short-lived, low transcriptional activity, and terminally differentiated homogeneous leucocytes that failed to return to circulation from tissue. Read More

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FGD5-AS1 Inhibits Osteoarthritis Development by Modulating miR-302d-3p/TGFBR2 Axis.

Cartilage 2021 Apr 9:19476035211003324. Epub 2021 Apr 9.

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

Objective: Osteoarthritis (OA) is a common joint disorder, accompanied by extracellular matrix (ECM) degradation. Reportedly, long noncoding RNAs (lncRNAs) are involved in OA pathogenesis. However, the role of lncRNA FYVE, RhoGEF, and PH domain containing 5 antisense RNA 1 (FGD5-AS1) in OA development is still not fully clarified. Read More

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Determining MMP-2 and MMP-9 reductive activities of bovine and equine amniotic membranes homogenates using fluorescence resonance energy transfer.

Vet Ophthalmol 2021 Apr 9. Epub 2021 Apr 9.

Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Introduction: Matrix metalloproteinases (MMPs)-2 and -9 are present in corneal ulcers, and an imbalance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) leads to further corneal degradation. Amniotic membrane homogenate (AMH) has proteolytic properties beneficial for corneal healing, but it is unknown whether AMH possesses TIMPs or effectively inhibits MMP-2 and MMP-9 activity.

Objective: To determine if bovine and equine AMH reduce in vitro MMP-2 and MMP-9 activities associated with the presence of TIMPs. Read More

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Lead Borate Nanoparticles Induce Apoptotic Gene Activity in P53 Mutant Cancer Cells.

Biol Trace Elem Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 26 Ağustos Campus, Kayisdagi cad., Kayisdagi, TR-34755, Istanbul, Turkey.

Cancer is a complex and multistage disease that causes suffering worldwide. Several mutations in tumor suppressor proteins are mostly responsible for tumorigenic development. Thus, determination of the mutations and developing a mutation targeted therapy are crucial in order to cure cancer. Read More

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