The Effect of Bromelain (Anaheal) on Clinical and Para-Clinical Parameters in Hospitalized COVID-19 Patients

The severity of COVID-19 disease and its mortality may be due to a localized vascular problem owing to the activation of bradykinin B1 receptors on endothelial cells in the lungs that occur following inflammation. Bromelain acts as an anti-inflammatory factor and can lower the level of bradykinin in the serum and tissues. Patients with the novel coronavirus (COVID-19) referred to Masih Daneshvari Hospital in Tehran were included in the study after providing full explanations and obtaining written consent. The 40 patients with mild to moderate symptoms were randomly divided into the control group (No: 20) and sample (No: 20). In the sample group, a dose of 200 mg bromelain was given to patients every 8 hours. In the control group, placebo capsules were administered exactly at the above intervals. Clinical and paraclinical factors (including SaO2, RR body temperature, MAP, HR, CRP, ESR, AST, ALT, Bil, BUN, Cr, WBC, Lymph, LDH, Plt were evaluated on a regular basis for up to five days. The results were evaluated using t-test and SPSS21 software. After treatment, the sample (Bromelain) group indicated significant improvement in SaO2, RR, HR, AST, ALT, BUN, ESR, LDH, and WBC and Lymphocyte count (P<0.05). Other factors did not have a significant difference with the control group. Bromelain causes improvement in some clinical symptoms such as respiratory parameters and para clinical items of mild to moderate hospitalized COVID-19 patients, so it can be a promising treatment. Furthered evaluation of larger groups is recommended.

A Multimodal Theranostic System Prepared from High-Density Lipoprotein Carrier of Doxorubicin and 177Lu

Recently, it was demonstrated that doxorubicin (Dox.HCl), a chemotherapeutic agent, could be photoactivated by Cerenkov radiation (CR). The objective of the present work was to develop a multimodal chemotherapy-radiotherapy-photodynamic therapeutic system based on reconstituted high-density lipoprotein (rHDL) loaded with Dox.HCl and 177Lu-DOTA. 177Lu acts as a therapeutic radionuclide and CR source. The system can be visualized by nuclear imaging. Fluorescence microscopy showed that rHDL-Dox specifically recognized cancer cells (T47D) that are positive for SR-B1 receptors. Encapsulated Dox.HCl was released into the cells and produced reactive oxygen species when irradiated with a 450-nm laser (photodynamic effect). The same effect occurred when Dox.HCl was irradiated by 177Lu CR. Through in vitro experiments, it was confirmed that the addition of 177Lu-DOTA to the rHDL-Dox nanosystem did not affect the specific recognition of SR-B1 receptors expressed in cells, or the cellular internalization of 177Lu-DOTA. The toxicity induced by the rHDL-Dox/177Lu nanosystem in cell lines with high (T47D and PC3), poor (H9C2) and almost-zero (human fibroblasts (FB)) expression of SR-B1 was evaluated in vitro and confirmed the synergy of the combined chemotherapy-radiotherapy-photodynamic therapeutic effect; this induced toxicity was proportional to the expression of the SR-B1 receptor on the surface of the cells used. The HDL-Dox/177Lu nanosystem experienced uptake by tumor cells and the liver-both tissues with high expression of SR-B1 receptors-but not by the heart. 177Lu CR offered the possibility of imparting photodynamic therapy where laser light could not reach.

The β-cell primary cilium is an autonomous Ca2+ compartment for paracrine GABA signalling

The primary cilium is an organelle present in most adult mammalian cells and is thought of as an antenna for detection of a variety of signals. Here we use intact mouse pancreatic islets of Langerhans to investigate signalling properties of the primary cilium in β-cells. Using cilia-targeted Ca2+ indicators we find that the resting Ca2+ concentration in the cilium is lower than that of the cytosol, and we uncover a Ca2+ extrusion mechanism in the cilium that effectively insulates the cilium from changes in cytosolic Ca2+. Stimuli that give rise to pronounced cytosolic Ca2+ concentration increases, such as glucose- and depolarization-induced Ca2+ influx, and mobilization of Ca2+ from the ER, was accompanied by minor increases in cilia Ca2+ concentrations that were spatially restricted to a small compartment at the base. Conversely, we observe pronounced Ca2+ concentration changes in the primary cilia of islet β-cells that do not propagate into the cytosol and show that paracrine GABA signalling via cilia-localized GABA- B1-receptors is responsible for this Ca2+ signalling. Finally, we demonstrate that the cilia response to GABA involves ligand-dependent transport of GABA-B1 receptors into the cilium.

Ace inhibitors - activators of kinin receptors

Angiotensin converting enzyme (ACE) inhibitors are widely used for treatment of cardiovascular diseases. The effects of ACE inhibitors on the human bradykinin receptors were investigated. The mode of action of ACE inhibitors is considered. There is evidence that ACE inhibitors exert effects on the vascular system that cannot be attributed simply to the inhibition of ACE activity and accumulation of locally produced bradykinin. ACE inhibitors augment bradykinin effects on receptors indirectly by inducing cross-talk between ACE and the B2 receptor when enzyme and receptor molecules are sterically close, possibly forming a heterodimer. ACE inhibitors activate B1 receptors directly and independently of ACE via the zink-binding consensus sequence HEXXH, which is present in B1, but not in B2 receptor. Particular structure of B2 and B1 are represented, as well as receptor amino acids coupled with the G-proteins. Activation of kinin receptors by ACE inhibitors leads to clinically beneficial effects of ACE inhibitors.