Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway.

Mitochondrial dysfunction is a hallmark of cellular senescence. Here, we investigated whether senescent cells release mitochondrial (mt)DNA into the extracellular space and its impact on innate immunity. We found that both primary senescent cells and tumor cells undergoing therapy-induced senescence actively released mtDNA into the extracellular environment.

Caprine dermal scaffolds for repair of full-thickness skin wounds in rabbits.

Biological scaffolds prepared after decellularization are used for the restoration of damaged tissues. A number of chemicals are used for bioscaffold preparation, and some of them damage their composition and architecture. Herein, we investigated the Sapindus mukorossi fruit pericarp extract (SPE) (5%) for decellularization of the caprine dermis.

A holistic review on trend, occurrence, factors affecting pesticide concentration, and ecological risk assessment.

Demographic outbursts and increased food demands invoke excessive use of pesticides in the agricultural field for increasing productivity which leads to the relentless decline of riverine health and its tributaries. These tributaries are connected to a plethora of point and non-point sources that transport pollutants including pesticides into the Ganga river's mainstream. Simultaneous climate change and lack of rainfall significantly increase pesticide concentration in the soil and water matrix of the river basin.

A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats.

Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease.

Dynein light chain binding determines complex formation and posttranslational stability of the Bcl-2 family members Bmf and Bim.

The BH3-only class of Bcl-2 family proteins triggers mitochondrial apoptosis. Several mechanisms are used to restrain the pro-apoptotic activity of these proteins. Dynein light chain (DYNLL) 1 and 2 has been proposed to negatively regulate the activity of Bim and Bmf, respectively, and the Bim-DYNLL1 interaction leads to the formation of large protein complexes on mitochondria.

The established and the predicted roles of dynein light chain in the regulation of mitochondrial apoptosis.

The mitochondrial pathway of apoptosis is regulated by the interplay between the members of Bcl-2 family. Within this family, BH3-only proteins are the sensors of apoptotic stimuli and can trigger apoptosis either by inhibiting the anti-apoptotic Bcl-2-family proteins or by directly activating the effectors Bax and Bak. An expanding body of research suggests that a number of non-Bcl-2 proteins can also interact with Bcl-2 proteins and contribute to the decision of cell fate.

Apoptotic and Immunosuppressive Effects of Turmeric Paste on 7, 12 Di Methyl Benz (a) Anthracene Induced Skin Tumor Model of Wistar Rat.

Dietary components with potent anticancerous property are gaining attention as therapeutic agents due to low cost of therapy and minimal toxic effects. Turmeric is one such miracle spices of Indian and South Asian recipes with multiple medicinal properties. The anticarcinogenic properties of its active compound curcumin have been studied in detail.

Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis.

The Bcl-2 family protein Bim triggers mitochondrial apoptosis. Bim is expressed in nonapoptotic cells at the mitochondrial outer membrane, where it is activated by largely unknown mechanisms. We found that Bim is regulated by formation of large protein complexes containing dynein light chain 1 (DLC1).

HN protein of Newcastle disease virus sensitizes HeLa cells to TNF-α-induced apoptosis by downregulating NF-κB expression.

Hemagglutinin neuraminidase (HN) is a membrane protein of Newcastle disease virus (NDV) with the ability to induce apoptosis in many transformed cell lines. TNF-α is a multi-factorial protein that regulates cell survival, differentiation and apoptosis. In a previous study, we reported that HN protein induces apoptosis by downregulating NF-κB expression.

G1-4A, a Polysaccharide from Tinospora cordifolia Inhibits the Survival of Mycobacterium tuberculosis by Modulating Host Immune Responses in TLR4 Dependent Manner.

Rapid emergence of drug resistance in Mycobacterium tuberculosis (MTB) is a major health concern and demands the development of novel adjunct immunotherapeutic agents capable of modulating the host immune responses in order to control the pathogen. In the present study, we sought to investigate the immunomodulatory effects of G1-4A, a polysaccharide derived from the Indian medicinal plant Tinospora cordifolia, in in-vitro and aerosol mouse models of MTB infection. G1-4A treatment of MTB infected RAW264.

The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances apoptosis.

Bim is a pro-apoptotic Bcl-2 family member of the BH3-only protein subgroup. Expression levels of Bim determine apoptosis susceptibility in non-malignant and in tumour cells. Bim protein expression is downregulated by proteasomal degradation following ERK-dependent phosphorylation and ubiquitination.

HN Protein of Newcastle Disease Virus Induces Apoptosis Through SAPK/JNK Pathway.

Many viral proteins are responsible for causing induction of apoptosis in the target cells. Hemagglutinin neuraminidase (HN), a multifunctional protein of Newcastle disease virus (NDV), is one of such proteins. The present study was undertaken to determine the apoptotic potential of the HN gene in cultured human cervical cancer cell line (HeLa cell) and to elucidate the molecular mechanisms involved.

Administration of IκB-kinase inhibitor PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats.

Nuclear factor kappa-B (NF-κB), a key anti-apoptotic factor, plays a critical role in tumor cell growth, metastasis, and angiogenesis. The transcriptional activity of NF-κB is normally suppressed in the cytoplasm due to its association with a natural inhibitor molecule IκB. Phosphorylation of the IκB at Ser 32 and Ser 36 by the IκB kinase complex (IKK) marks the degradation of the molecule by 26S proteasome.

Regulation of Liver Enriched Transcription Factors in Rat Hepatocytes Cultures on Collagen and EHS Sarcoma Matrices.

Liver-enriched transcription factors (LETF) play a crucial role in the control of liver-specific gene expression and for hepatocytes to retain their molecular and cellular functions complex interactions with extra cellular matrix (ECM) are required However, during cell isolation ECM interactions are disrupted and for hepatocytes to regain metabolic competency cells are cultured on ECM substrata. The regulation of LETFs in hepatocytes cultured on different ECM has not been studied in detail. We therefore compared two common sources of ECM and evaluated cellular morphology and hepatocyte differentiation by investigating DNA binding activity of LETFs at gene specific promoters and marker genes of hepatic metabolism.

Apoptin as a potential viral gene oncotherapeutic agent.

The use of viruses for treatment of cancer overcomes the bottlenecks of chemotherapy and radiotherapy. Several viruses and their proteins have been evaluated for oncolytic effect. The VP3 protein (apoptin) of chicken anemia virus is one such protein with an inherent ability to lyse cancer and transformed cells while leaving normal cells unharmed.

In-vitro characterization and evaluation of apoptotic potential of bicistronic plasmid encoding HN gene of Newcastle disease virus and human TNF-α.

The viral gene oncotherapy in combination with cytokines emerges as an exciting strategy for cancer therapy due to its minimal side effects and tumor specificity. HN is the surface protein of NDV which is involved in virus infectivity and is known to kill many cancerous cell types. TNF-α, a multifactorial cytokine has direct anti-tumor activity by activating the extrinsic pathways of apoptosis.

Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations.

Recent advances in live cell imaging of hepatoma cells.

Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer.

A rat toxicogenomics study with the calcium sensitizer EMD82571 reveals a pleiotropic cause of teratogenicity.

The calcium sensitizer and PDEIII inhibitor EMD82571 caused exencephaly, micrognathia, agnathia and facial cleft in 58% of fetuses. In pursue of mechanisms and to define adverse outcome pathways pregnant Wistar rats were dosed daily with either EMD82571 (50 or 150mg/kg/day) or retinoic acid (12mg/kg/day) on gestational days 6-11 and 6-17, respectively. Hypothesis driven and whole genome microarray experiments were performed with whole embryo, maternal liver, embryonic liver and malformed bone at gestational days 12 and 20.

How useful are clinical liver function tests in in vitro human hepatotoxicity assays?

In preclinical hepatotoxicity testing cell based assays are frequently employed. However, prediction of clinical drug induced liver injury (DILI) remains a major challenge. Here we examined the usefulness of frequently employed markers of hepatocellular injury in cultures of primary human hepatocytes (PHH) in response to treatment with either paracetamol, rifampicin, petadolex and/or amiodarone.

Canine parvovirus type 2a (CPV-2a)-induced apoptosis in MDCK involves both extrinsic and intrinsic pathways.

The canine parvovirus type 2 (CPV-2) causes an acute disease in dogs. It has been found to induce cell cycle arrest and DNA damage leading to cellular lysis. In this paper, we evaluated the apoptotic potential of the "new CPV-2a" in MDCK cells and elucidated the mechanism of the induction of apoptosis.

Oncolytic viruses & their specific targeting to tumour cells.

Cancer is one of the major causes of death worldwide. In spite of achieving significant successes in medical sciences in the past few decades, the number of deaths due to cancer remains unchecked. The conventional chemotherapy and radiotherapy have limited therapeutic index and a plethora of treatment related side effects.

Prokaryotic expression of chicken infectious anemia apoptin protein and characterization of its polyclonal antibodies.

In the present study recombinant VP3 (rVP3) was expressed in E. coli BL21 (DE3) (pLysS) and its polyclonal antibodies were characterized. SDS-PAGE analysis revealed that the expression of recombinant protein was maximum when induced with 1.

Characterization and in vitro expression of non-structural 1 protein of canine parvovirus (CPV-2) in mammalian cell line.

Parvoviruses are small, 260-A-diameter, icosahedral, non-enveloped, single-stranded DNA viruses with a genome of approximately 5 kb. Non structural protein, (NS-1) is especially relevant, being both essential for virus replication and the main factor responsible for virus pathogenicity and cytotoxicity. This protein has also been reported to possess the property of killing of transformed cells.