Corrigendum: Sesquiterpene lactones attenuate paclitaxel resistance via inhibiting MALAT1/STAT3/ FUT4 axis and P-Glycoprotein transporters in lung cancer cells.

[This corrects the article DOI: 10.3389/fphar.2022.795613.].

Toxicological effects of dimethlybenzeneanthracene in Balb C mice and pharmacological intervention by silk sericin-conjugated silver nanoparticles.

Polycyclic aromatic hydrocarbons (PAHs) such as 7, 12-dimethylbenzneanthracene (DMBA), due to long-term bioaccumulation cause serious physiological processes and behavioral dysfunctions such as cancer, ageing, and hypertension. Silk sericin (SS) is instrumental in cancer applications due to presence of flavonoids and carotenoids which are natural pigments, present in the layer of sericin that has antioxidant and antityrosinase activity. It reduces oxidative stress and suppresses cancer cytokines while interacting with reactive oxygen species (ROS) to stand against lipid peroxidation. Recent research was focused to calculate the pharmacological intervention of sericin-conjugated silver nanoparticles (S-AgNO3 NPs) against DMBA-induced toxicity. For this purpose, SS protein was extracted from silkworm cocoons by degumming process and the prepared S-AgNO3 NPs via a green synthesis. In female albino mice, a total of 50 mg/kg oral administration of DMBA was used for the induction of toxicity which required almost 8 to 10 weeks approximately. After 60 days of experimentation, mice were dissected, blood samples were collected for further hematological and biochemical analysis and were euthanized via cervical dislocation. There was a significant rise in the level of red blood cells, platelets, lymphocytes, and hemoglobin at the highest applied concentration of sericin and its nanoparticles. Similarly, a reasonable decline was observed in the level of white blood cells, neutrophils, eosinophils, and monocytes as compared to the cancer-inducing group. The level of glutathione, lactate dehydrogenase, and alkaline phosphatase as well as immunoglobulins such as immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) were significantly reduced in all treatment groups as compared to the DMBA-induced group. Substantial effects were demonstrated in response to S-AgNO3 NPs II (T) at the highest concentrations (200 mg/kg, BW) as follows: glutathione (2.42 ± 0.26 µmol/L), lactate dehydrogenase (493.6 ± 5.78 U/L), alkaline phosphatase (158.4 ± 6.35 U/L), IgA (4.22 ± 0.19 g/L), IgG (70 ± 1.70 g/L), and IgM (4.76 ± 0.12). The histopathological study of the liver, kidneys, and brain revealed that the DMBA-induced group showed cytotoxic effects against all selected organs of mice that were recovered by treatment of selective compounds but highly effective recovery was seen in S-AgNO3 NPs II (T). These results concluded that silk S-AgNO3 NPs showed significant pharmacological potential against cancer-inducing toxicity.

Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells.

Paclitaxel resistance is a challenging factor in chemotherapy resulting in poor prognosis and cancer recurrence. Signal transducer and activator of transcription factor 3 (STAT3), a key transcription factor, performs a critical role in cancer development, cell survival and chemoresistance, while its inactivation overwhelms drug resistance in numerous cancer types including lung cancer. Additionally, the fucosyltransferase 4 (FUT4) is a crucial enzyme in post-translational modification of cell-surface proteins involved in various pathological conditions such as tumor multidrug resistance (MDR). The P-glycoprotein (P-GP) is the well-known ABC transporter member that imparts drug resistance in different cancer types, most notably paclitaxel resistance in lung cancer cells. LncRNA-MALAT1 exerts a functional role in the cancer development as well as the drug resistance and is linked with STAT3 activation and activity of FUT4. Moreover, STAT3-mediated induction of P-GP is well-documented. Natural compounds of Sesquiterpene Lactone (SL) family are well-known for their anticancer properties with particular emphasis over STAT3 inhibitory capabilities. In this study, we explored the positive correlation of MALAT1 with STAT3 and FUT4 activity in paclitaxel resistant A549 (A549/T) lung cancer cells. Additionally, we investigated the anticancer activity of two well-known members of SLs, alantolactone (ALT) and Brevilin A (Brv-A), in A549/T lung cancer cells. ALT and Brv-A induced apoptosis in A549/T cells. Furthermore, these two natural SLs suppressed MALAT1 expression, STAT3 activation, and FUT4 and P-GP expression which are the hallmarks for paclitaxel resistance in A549 lung cancer cells. The inhibition of MALAT1 enhanced the competence of these SLs members significantly, which accounted for the growth inhibition as well as anti-migratory and anti-invasive effects of ALT and Brv-A. These findings suggest SLs to be the promising agents for overcoming paclitaxel resistance in A549 lung cancer cells.

Current status of beta-thalassemia and its treatment strategies.

BACKGROUND: Thalassemia is an inherited hematological disorder categorized by a decrease or absence of one or more of the globin chains synthesis. Beta-thalassemia is caused by one or more mutations in the beta-globin gene. The absence or reduced amount of beta-globin chains causes ineffective erythropoiesis which leads to anemia. METHODS: Beta-thalassemia has been further divided into three main forms: thalassemia major, intermedia, and minor/silent carrier. A more severe form among these is thalassemia major in which individuals depend upon blood transfusion for survival. The high level of iron deposition occurs due to regular blood transfusion therapy. RESULTS: Overloaded iron raises the synthesis of reactive oxygen species (ROS) that are noxious and prompting the injury to the hepatic, endocrine, and vascular system. Thalassemia can be analyzed and diagnosed via prenatal testing (genetic testing of amniotic fluid), blood smear, complete blood count, and DNA analysis (genetic testing). Treatment of thalassemia intermediate is symptomatic; however; it can also be accomplished by folic supplementation and splenectomy. CONCLUSION: Thalassemia major can be cured through regular transfusion of blood, transplantation of bone marrow, iron chelation management, hematopoietic stem cell transplantation, stimulation of fetal hemoglobin production, and gene therapy.