P-type calcium ATPases play important roles in biotic and abiotic stress signaling.

MAIN CONCLUSION: Knowledge of Ca2+-ATPases is imperative for improving crop quality/ food security, highly threatened due to global warming. Ca2+-ATPases modulates calcium, essential for stress signaling and modulating growth, development, and immune activities. Calcium is considered a versatile secondary messenger and essential for short- and long-term responses to biotic and abiotic stresses in plants. Coordinated transport activities from both calcium influx and efflux channels are required to generate cellular calcium signals. Various extracellular stimuli cause an induction in cytosolic calcium levels. To cope with such stresses, it is important to maintain intracellular Ca2+ levels. Plants need to evolve efficient efflux mechanisms to maintain Ca2+ ion homeostasis. Plant Ca2+-ATPases are members of the P-type ATPase superfamily and localized in the plasma membrane and endoplasmic reticulum (ER). They are required for various cellular processes, including plant growth, development, calcium signaling, and even retorts to environmental stress. These ATPases play an essential role in Ca2+ homeostasis and are actively involved in Ca2+ transport. Plant Ca2+-ATPases are categorized into two major classes: type IIA and type IIB. Although these two classes of ATPases share similarities in protein sequence, they differ in their structure, cellular localization, and sensitivity to inhibitors. Due to the emerging role of Ca2+-ATPase in abiotic and biotic plant stress, members of this family may help promote agricultural improvement under stress conditions. This review provides a comprehensive overview of P-type Ca2+-ATPase, and their role in Ca2+ transport, stress signaling, and cellular homeostasis focusing on their classification, evolution, ion specificities, and catalytic mechanisms. It also describes the main aspects of the role of Ca2+-ATPase in transducing signals during plant biotic and abiotic stress responses and its role in plant development and physiology.

Does Mucosal Chronic Otitis Media Leads to Sensorineural Hearing Loss.

Sensori-neural hearing loss (SNHL) results from inner ear damage or injury to the neural pathways that relay signals from the inner ear to the brain. A serious sequelae of COM is damage to the inner ear. This study aimed at finding the occurrence of SNHL in unilateral mucosal COM. One Hundred patients who had unilateral mucosal COM were enrolled in the study and underwent pure tone audiometry using Audio 4002 system in acoustically treated room. Bone conduction (BC) threshold less than 20 dB was taken as normal. Significant SNHL of 23% was seen in mucosal COM. Unilateral mucosal COM leads to significant impact on BC thresholds. The risk of SNHL increases with larger perforation size and increasing duration and active stage of disease.

Natural products and their derivatives as immune check point inhibitors: Targeting cytokine/chemokine signalling in cancer.

Cancer immunotherapy is the new generation and widely accepted form of tumour treatment. It is, however, associated with exclusive challenges which include organ-specific inflammation, and single-target strategies. Therefore, approaches that can enhance the efficiency of existing immunotherapies and expand their indications are required for the further development of immunotherapy. Natural products and medicines are stated to have this desired effect on cancer immunotherapy (adoptive immune-cells therapy, cancer vaccines, and immune-check point inhibitors). They refurbish the immunosuppressed tumour microenvironment, which is the primary location of interaction of tumour cells with the host immune system. Various immune cell subsets, via interaction with cytokine/chemokine receptors, are recruited into this microenvironment, and these subsets have roles in tumour progression and treatment responsiveness. This review summarises cytokine/chemokine signalling, types of cancer immunotherapy and the herbal medicine-derived natural products targeting cytokine/chemokines and immune checkpoints. These natural compounds possess immunomodulatory activities and exert their anti-tumour effect by either blocking the interaction or modulating the expression of the proteins linked with immune checkpoint signaling pathways. Some compounds also show a synergistic effect in combination with existing monoclonal antibody drugs to reverse the tumour microenvironment. Additionally, we have also reported some studies about the derivatives and formulations used to overcome the limitations of natural forms. This review can provide important insights for directing future research.

Aberrant Lighting Causes Anxiety-like Behavior in Mice but Curcumin Ameliorates the Symptoms.

In the modern research field, laboratory animals are constantly kept under artificial lighting conditions. However, recent studies have shown the effect of artificial light on animal behavior and metabolism. In the present study on mice, following three weeks of housing in dim light at night (dLAN; 5lux) and complete darkness (DD; 0lux), we monitored the effect on body weight, daily food intake, anxiety-like behavior by employing the open field test, and expression of the period (PER1) gene. We also studied the effect of oral administration of different concentrations of curcumin (50, 100, and 150 mg/kg) for three weeks in the same mice and monitored these parameters. The exposure to dLAN had significantly increased the anxiety-like behavior and body weight possibly through the altered metabolism in mice, whereas exposure to DD caused increased anxiety but no significant difference in weight gain. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on body weight, it ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, alteration in the light/dark cycle had a negative effect on laboratory animals on the body weight and emotions of animals. The present study identifies the risk factors associated with artificial lighting systems on the behavior of laboratory animals and the ameliorative effects of curcumin, with a focus on anxiety-like behavior.

Dim Light at Night Induced Neurodegeneration and Ameliorative Effect of Curcumin.

It is a well-known fact that following a proper routine light/dark or diurnal rhythm controls almost all biological processes. With the introduction of modern lighting and artificial illumination systems, continuous exposure to light at night may lead to the disruption of diurnal rhythm. However, the effect of light during the night on brain anatomy, physiology, and human body functions is less explored and poorly understood. In this study, we have evaluated the effect of exposure to dim light (5 lux) at night (dLAN) on Swiss Albino mice over a duration of three consecutive weeks. Results have revealed that exposure to dLAN led to an impairment of cognitive and non-cognitive behaviour, oxidative stress-mediated elevation of lipid peroxidation, and reduction of superoxide dismutase and catalase activity. It also led to the downregulation of hippocampal proteins (BDNF, Synapsin II and DCX) at both protein and mRNA level. Additionally, there was downregulation of CREB and SIRT1 mRNAs and neurodegeneration-associated miRNA21a-5p and miRNA34a-5p. The pyramidal and cortical neurons started showing pyknotic and chromatolysis characteristics. However, a dose of curcumin administered to the mice positively modulated these parameters in our experimental animals. We proposed the modulatory role of curcumin in addressing the deleterious effects of dLAN.

Role of microRNA and Long Non-Coding RNA in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for about 80-90% of all liver cancers and is found to be the third most common cause of cancer mortality in the Asia-Pacific region. Risk factors include hepatitis B and C virus, cirrhosis, aflatoxin-contaminated food, alcohol, and diabetes. Surgically removing the tumor tissue seems effective but a high chance of recurrence has led to an urgent need to develop novel molecules for the treatment of HCC. Clinical management with sorafenib is found to be effective but it is only able to prolong survival for a few months. Various side effects like gastrointestinal and abdominal pain, hypertension, and hemorrhage are also associated with sorafenib, which calls for the unmet need of effective therapies against HCC. Similarly, the genetic mechanisms behind the occurrence of HCC are still unknown and need to be expounded further for developing newer candidates. Since unearthing the concept of these variants, transcriptomics has revealed the role of noncoding RNAs (ncRNAs) in many cellular, physiological and pathobiological processes. They are also found to be widely associated and abundantly expressed in a variety of cancer. Aberrant expression and mutations are closely related to tumorigenesis and metastasis and hence are classified as novel biomarkers and therapeutic targets for the treatment of cancer, including HCC. Herein, this review summarises the relationship between ncRNAs and hepatocellular carcinoma.

Role of Host and Pathogen-Derived MicroRNAs in Immune Regulation During Infectious and Inflammatory Diseases.

MicroRNAs (miRNAs, miRs) are short, endogenously initiated, non-coding RNAs that bind to target mRNAs, leading to the degradation or translational suppression of respective mRNAs. They have been reported as key players in physiological processes like differentiation, cellular proliferation, development, and apoptosis. They have gained importance as gene expression regulators in the immune system. They control antibody production and release various inflammatory mediators. Abnormal expression and functioning of miRNA in the immune system is linked to various diseases like inflammatory disorders, allergic diseases, cancers etc. As compared to the average human genome, miRNA targets the genes of immune system quite differently. miRNA appeared to regulate the responses related to both acquired and innate immunity of the humans. Several miRNAs importantly regulate the transcription and even, dysregulation of inflammation-related mediators. Many miRNAs are either upregulated or downregulated in various inflammatory and infectious diseases. Hence, modifying or targeting the expression of miRNAs might serve as a novel strategy for the diagnosis, prevention, and treatment of various inflammatory and infectious conditions.