Cancer is a current dreadful disease and the leading cause of death. Next to cardiovascular diseases, cancer is the most severe threat to human life and health. Breast cancer is the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed the biocompatible nanomaterials, CNTs-HAP and GR-HAP, through grafting of hydroxyapatite (HAP) to carbon nanotubes (CNTs) and graphene (GR) nanosheets. CNTs-HAP and GR-HAP have been tested for their cytotoxicity, growth and motility inhibitory effects, and their effects on the mesenchymal markers. All these demonstrated significant dose-dependent and time-dependent in vitro cytotoxicity against SUM-159 and MCF-7 breast cancer cell lines. The cell viability assay showed that the CNTs-HAP was more effective over SUM-159 cells than MCF-7 cells. It found that the increase in the concentration of GR-HAP has inhibited the clonogenic ability of breast cancer cells. The GR-HAP exhibited a substantial inhibitory effect on the cell motility of SUM-159 cell lines. It was investigated that the expression of vimentin (mesenchymal marker) was majorly reduced in SUM-159 cells by GR-HAP.

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated and identified the impact of CRD on basal tumorigenesis and mammary gland morphology. We found that chronic CRD disrupted mammary gland morphology, increased lung metastasis, and induced an immunosuppressive tumor microenvironment by enhancing LILRB4 expression. Furthermore, targeted immunotherapy against LILRB4 reduced CRD-induced immunosuppressive microenvironment and lung metastasis. Finally, we showed that LILRB4 regulates CRD-induced mammary tumorigenesis via a non-canonical WNT signaling pathway. These findings identify and implicate LILRB4 as a link between CRD and aggressive mammary tumorigenesis and establish the potential role of the targeted LILRB4a immunotherapy as an inhibitor of CRD-induced lung metastasis.

Thyroid disorders have been one among the most challenging and most common endocrine disorders that we confront worldwide. Major thyroid disorders include hypothyroidism, hyperthyroidism, goiter/iodine deficiency, Hashimoto's thyroiditis, and thyroid cancer. Among these, hypothyroidism is arguably the most challenging as its multifarious clinical presentation often goes unnoticed. Hypothyroidism can be attributed to the deficiency of thyroid hormones, triiodothyronine (T3) and thyroxine (T4), in the body. Mild or subclinical hypothyroidism refers to the condition where peripheral thyroid hormone levels are within normal range, but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. Data to date are scarce that include direct experimental, pharmacological, or preclinical types of evidence of treating hypothyroidism with Ayurvedic and herbal drugs. The scope of this manuscript covers the utility of conventional Ayurveda or herbal drugs in ameliorating the pathophysiological symptoms of hypothyroidism. Treatment strategies have been evolving since the early and mid-twentieth century, starting from using the whole thyroid extract to the modern-day thyroxine monotherapy by L-thyroxine. Despite these advances, there remains a considerably large population who endure the symptoms of hypothyroidism. Various assortments of formulations are available for such conditions in Ayurveda system of medicine since the very early days of civilization. In Ayurveda, though there are not any direct reference of thyroid, Galaganda and Gandamala, which possess symptomatic similarities with thyroid disorders, have been mentioned frequently in the texts. With the present data available, it is concluded that natural resources around can be utilized for the prevention and amelioration of hypothyroidism in mammals.

Epidemiological studies have shown that circadian rhythm disruption (CRD) caused by shift work or frequent jet lag is associated with the risk of breast cancer development. However, the role of CRD in mammary gland morphology and aggressive mammary tumorigenesis and the molecular mechanisms underlying CRD and cancer risk remain unknown. We found that chronic CRD disrupted mouse mammary gland morphology and increased tumor burden and lung metastasis in a genetically engineered mouse model of aggressive breast cancer and induced an immunosuppressive tumor microenvironment by enhancing leukocyte immunoglobulin-like receptor 4a (LILRB4a or LILRB4) expression. Moreover, CRD increased the M2 macrophage (anti-inflammatory) and regulatory T-cell populations but decreased the M1 macrophage (proinflammatory) populations. These findings identify and implicate LILRB4a as a link between CRD and aggressive mammary tumorigenesis. Teaser Circadian rhythm disruption enhances aggressive mammary tumorigenesis by elevating LILRB4a expression.