Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles.

Elicitors fortifies the plant resilience against metal and metalloid stress.

This review addresses plant interactions with HMs, emphasizing defence mechanisms and the role of chelating agents, antioxidants and various elicitor molecules in mitigating metal toxicity in plants. To combat soil contamination with HMs, chelate assisted phytoextraction using application of natural or synthetic aminopolycarboxylic acids is an effective strategy. Plants also employ diverse signaling pathways, including hormones, calcium, reactive oxygen species, nitric oxide, and Mitogen-Activated Protein Kinases influencing gene expression and defence mechanisms to counter HM stress.

Enhanced CTLA-4 blockade anti-tumor immunity with APG-157 combination in a murine head and neck cancer.

Background: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors.

Methods: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies.

Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.

Unlabelled: Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination.

Revelations on photosystem II, thermoluminescence, and artificial photosynthesis: a retrospective of Govindjee from fundamentals to applications.

Photosynthesis, as one of the most important chemical reactions, has powered our planet for over four billion years on a massive scale. This review summarizes and highlights the major contributions of Govindjee from fundamentals to applications in photosynthesis. His research included primary photochemistry measurements, in the picosecond time scale, in both Photosystem I and II and electron transport leading to NADP reduction, using two light reactions.

Acidification of intracellular pH in MM tumor cells overcomes resistance to hypoxia-mediated apoptosis and .

Introduction: Multiple myeloma (MM) is an incurable cancer of malignant plasma cells that engraft in the bone marrow (BM). It is more than likely that the poorly investigated physical parameters of hypoxia and pH in the tumor microenvironment (TME) is critical for MM survival. Here, we explore the effects of a hypoxic environment on pH regulation and its role in MM survival.

Barriers to seeking treatment for alcohol use disorders among males in a tertiary care center in South India - a cross-sectional study.

Background: There are limited studies on barriers to seeking treatment for Alcohol Use Disorders (AUD) among males in tertiary care centers in India and abroad. Identification of these factors can aid in addressing the barriers to seeking treatment for AUD in low-and-middle-income countries.

Objective: To investigate the barriers to seeking treatment for AUD among males in a tertiary care center in South India.

Auditory Speech Based Alerting System for Detecting Dummy Number Plate via Video Processing Data sets.

Spectrum of applications in computer vision use object detection algorithms driven by the power of AI and ML algorithms. State of art detection models like faster Region based convolutional Neural Network (RCNN), Single Shot Multibox Detector (SSD), and You Only Look Once (YOLO) demonstrated a good performance for object detection, but many failed in detecting small objects. In view of this an improved network structure of YOLOv4 is proposed in this paper.

Key Players of the Immunosuppressive Tumor Microenvironment and Emerging Therapeutic Strategies.

The tumor microenvironment (TME) is a complex, dynamic battlefield for both immune cells and tumor cells. The advent of the immune checkpoint inhibitors (ICI) since 2011, such as the anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 and anti-programmed cell death receptor (PD)-(L)1 antibodies, provided powerful weapons in the arsenal of cancer treatments, demonstrating unprecedented durable responses for patients with many types of advanced cancers. However, the response rate is generally low across tumor types and a substantial number of patients develop acquired resistance.

Seed nutripriming with zinc is an apt tool to alleviate malnutrition.

More than 2 billion people worldwide suffer from micronutrient malnutrition, sometimes known as hidden hunger. Zn malnutrition affects around a third of the world's population. The physicochemical features of soil, which limit the availability of Zn to plants, cause Zn deficiency.

Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?

Multiple myeloma (MM) is an incurable cancer arising from malignant plasma cells that engraft in the bone marrow (BM). The physiology of these cancer cells within the BM microenvironment (TME) plays a critical role in MM development. These processes may be similar to what has been observed in the TME of other (non-hematological) solid tumors.

Adipose-Derived Mesenchymal Stromal Cells Persist in Tissue-Engineered Vocal Fold Replacement in Rabbits.

Objectives:: Cell therapies using mesenchymal stromal cells (MSCs) have been proposed as a promising new tool for the treatment of vocal fold scarring. However, the mechanisms by which MSCs promote healing as well as their duration of survival within the host vocal fold have yet to be defined. The aim of this work was to assess the persistence of embedded MSCs within a tissue-engineered vocal fold mucosal replacement in a rabbit model of vocal fold injury.

Restoration of the prolyl-hydroxylase domain protein-3 oxygen-sensing mechanism is responsible for regulation of HIF2α expression and induction of sensitivity of myeloma cells to hypoxia-mediated apoptosis.

Multiple myeloma (MM) is an incurable disease of malignant plasma B-cells that infiltrate the bone marrow (BM), resulting in bone destruction, anemia, renal impairment and infections. Physiologically, the BM microenvironment is hypoxic and this promotes MM progression and contributes to resistance to chemotherapy. Since aberrant hypoxic responses may result in the selection of more aggressive tumor phenotypes, we hypothesized that targeting the hypoxia-inducible factor (HIF) pathways will be an effective anti-MM therapeutic strategy.

Utility of FNAC in Conjunction with Cell Block for Diagnosing Space-Occupying Lesion (SOL) of Liver with Emphasis on Differentiating Hepatocellular Carcinoma from Metastatic SOL: Analysis of 61 Cases.

Objectives: To study the cytological patterns of fine-needle aspiration cytology (FNAC) obtained from space-occupying lesions (SOLs) of the liver with an aim to differentiate primary hepatocellular carcinoma from metastatic deposits and to evaluate the added advantage and efficacy of studying cell blocks in conjunction with smears for enhancing diagnostic accuracy.  .

Methods: This prospective study took place over two years (September 2007 to 2009) and included 61 patients with cases of liver SOLs that were clinically or radiologically suspicious for malignancy and who were referred for computed tomography or ultrasonography-guided FNAC.

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB.

We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB.

Molecular cloning of a coiled-coil-nucleotide-binding-site-leucine-rich repeat gene from pearl millet and its expression pattern in response to the downy mildew pathogen.

Downy mildew caused by Sclerospora graminicola is a devastating disease of pearl millet. Based on candidate gene approach, a set of 22 resistance gene analogues were identified. The clone RGPM 301 (AY117410) containing a partial sequence shared 83% similarity to rice R-proteins.

Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.

Human immunodeficiency virus type 1 (HIV-1) isolates from India mainly belong to clade C and are quite distinct from clade C isolates from Africa in terms of their phylogenetic makeup, serotype, and sensitivity to known human broadly neutralizing monoclonal antibodies. Because many of these properties are associated with the envelope proteins of HIV-1, it is of interest to study the envelope proteins of Indian clade C isolates as part of the ongoing efforts to develop a vaccine against HIV-1. To this end, we purified trimeric uncleaved gp145 of a CCR5 tropic Indian clade C HIV-1 (93IN101) from the conditioned medium of 293 cells.

Evaluation of probiotic milk on salivary mutans streptococci count: an in vivo microbiological study.

Objective: The objective of the present study was to investigate the effect of probiotic Lactobacillus casei Shirota on the values of mutans streptococci counts in saliva.

Study Design: 31 children were included in this double blinded study. Study design included 4 periods which consisted of a run in period, two intervention periods and a washout period.

Immuno-affinity purification of PglPGIP1, a polygalacturonase-inhibitor protein from pearl millet: studies on its inhibition of fungal polygalacturonases and role in resistance against the downy mildew pathogen.

Polygalacturonase-inhibitor proteins (PGIPs) are important plant defense proteins which modulate the activity of microbial polygalacturonases (PGs) leading to elicitor accumulation. Very few studies have been carried out towards understanding the role of PGIPs in monocot host defense. Hence, present study was taken up to characterize a native PGIP from pearl millet and understand its role in resistance against downy mildew.

The pearl millet mitogen-activated protein kinase PgMPK4 is involved in responses to downy mildew infection and in jasmonic- and salicylic acid-mediated defense.

Plant mitogen-activated protein kinases (MPKs) transduce signals required for the induction of immunity triggered by host recognition of pathogen-associated molecular patterns. We isolated a full-length cDNA of a group B MPK (PgMPK4) from pearl millet. Autophosphorylation assay of recombinant PgMPK4 produced in Escherichia coli confirmed it as a kinase.

p16 Protein and gigaxonin are associated with the ubiquitination of NFκB in cisplatin-induced senescence of cancer cells.

The molecular mechanism of p16-mediated senescence in cisplatin-treated cancer cells is not fully understood. Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFκB. Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFκB interacting with its DNA binding sequences, leading to decreased expression of NFκB-transcribed proteins.

Correction: The CD44 Tumorigenic Subsets in Lung Cancer Biospecimens Are Enriched for Low miR-34a Expression.

[This corrects the article on p. e73195 in vol. 8.

The CD44(high) tumorigenic subsets in lung cancer biospecimens are enriched for low miR-34a expression.

Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states), and aggressive behavioral properties (including high tumorigenic potentials). We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC) can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE).

Hyperactivated JNK is a therapeutic target in pVHL-deficient renal cell carcinoma.

Clear cell renal cell carcinomas (RCC), the major histologic subtype of RCC accounting for more than 80% of cases, are typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Although accumulation of hypoxia-inducible factor alpha (HIF-α) is the most well-studied effect of VHL inactivation, direct inhibition of HIFα or restoration of wild-type pVHL protein expression has not proved readily feasible, given the limitations associated with pharmacologic targeting of transcription factors (i.e.