Current Pharmaceutical Design - Volume 28, Issue 42, 2022

Background: Pulmonary microbial infection is mainly caused by microbes like atypical bacteria, viruses, and fungi, on both the upper and lower respiratory tracts. One of the demands of the present is the use of nanotechnology-based treatments to fight various lung infections. Aim: The main aim of the study is to explore all pulmonary infectious diseases and to compare the advanced and novel treatment approaches with the conventional methods which are available to treat infections. Methods: This work sheds light on pulmonary infectious diseases with their conventional and present treatment approaches along with a focus on the advantageous roles of nano-based formulations. In the literature, it has been reported that the respiratory system is the key target of various infectious diseases which gives rise to various challenges in the treatment of pulmonary infections. Results: The present review article describes the global situation of pulmonary infections and the different strategies which are available for their management, along with their limitations. The article also highlights the advantages and different examples of nanoformulations currently combating the limitations of conventional therapies. Conclusion: The content of the present article further reflects on the summary of recently published research and review works on pulmonary infections, conventional methods of treatment with their limitations, and the role of nano-based approaches to combat the existing infectious diseases which will jointly help the researchers to produce effective drug formulations with desired pharmacological activities.

Background: Imbalances in dopamine levels result in neurological and psychological disorders such as elevated dopamine in Parkinson’s disease. Objective: Despite a considerable number of advertisements claiming Aloe-vera’s effectiveness in PD treatment, it has hidden long-term disadvantages for healthy people and PD patients. Methods: In the present investigation, the impacts of Aloe-vera on dopaminergic cells were evaluated. Results: The results indicated that the focal adhesion kinase (FAK) enhancement was in line with the Bax/Bcl2 ratio decrement, reactive oxygen specious (ROS) production, and nonsignificant alteration in the sub-G1phase of the cell cycle. It led to glial cell-derived neurotrophic factor (GDNF) upregulation but did not significantly change the BDNF level involved in depression and motor impairment recovery. These events apparently resulted in the enhancement in dopaminergic cell viability and neurite length and attenuated PI+ cells. However, it also induced neuronal nitric oxide synthase (nNOS) overexpression and nitric oxide (NO) and lactate dehydrogenase (LDH) production. Notably, docking results of the catalytic domain in tyrosine hydroxylase (TH) with the Aloe-vera constituents showed strong binding of most Aloe-vera constituents with the catalytic domain of TH, even stronger than L-tyrosine as an original substrate. Following the docking results, Aloe-vera downregulated TH protein and attenuated dopamine. Conclusion: It can be hypothesized that Aloe-vera improves PD symptoms through enhancement in antiapoptotic markers and neurotrophic factors, while it suppresses TH and dopamine in the form of a Trojan horse, later resulting in the future deterioration of the disease symptoms. The results provide cues to pharmaceutical companies to use the active components of Aloe-vera as putative agents in neurological and psychiatric disorders and diseases to decrease dopamine in patients with enhanced dopamine levels.

Background: Although the majority of members belonging to the small GTPase Ras superfamily have been studied in several malignancies, the function of RBJ has remained unclear, particularly in non-small cell lung cancer (NSCLC). Objective: The research aims to determine the function of RBJ in NSCLC. Methods: The levels of RBJ protein in tumor tissue and para-carcinoma normal tissue were ascertained via immunohistochemistry (IHC). The growth, migration, and invasion of NSCLC cells were assessed by 5- ethynyl-2-deoxyuridine (EdU) assay, colony formation, cell counting kit-8 (CCK8), transwell and wound healing assays. Furthermore, a nude mouse xenograft model was established to study the function of RBJ in tumorigenesis in vivo. Results: The IHC analysis revealed that the protein levels of RBJ were notably increased in tumor tissue and positively associated with the clinical stage. In addition, the knockdown of RBJ restrained the growth, invasion, and migration of NSCLC cell lines by inhibiting the epithelial-mesenchymal transition (EMT) through the MEK/ERK signaling pathway. Accordingly, opposite results were observed when RBJ was overexpressed. In addition, the overexpression of RBJ accelerated tumor formation by A549 cells in nude mice. Conclusion: RBJ promoted cancer progression in NSCLC by activating EMT via the MEK/ERK signaling. Thus, RBJ could be used as a potential therapeutic against NSCLC.

Background: The mechanism of Heat Shock Protein 90 (HSP90) in Ulcerative Colitis (UC) has been studied, and mitogenic-activated protein kinases (MAPK) also contribute to the pathogenesis of UC. However, the effect of the HSP90/MAPK pathway in UC is still unclear. Therefore, the mainstay of this research is to explore the mechanism of action of this pathway in UC. Compound sophorae decoction (CSD), as a Chinese herbal decoction, can synergistically affect the above process. Objective: This study aimed to uncover the synergistic effects of HSP90 inhibitors regulating the MAPK pathway for treating DSS-induced colitis in mice and the synergistic effects of CSD. Methods: This experiment used oral administration of standard diets containing 3% dextran sodium sulfate (DSS) to establish an experimental colitis model in mice. The model was treated with HSP90 inhibitor, CSD, or dexamethasone. Mouse feces, mobility, body weight, colon length, and colon histopathology scores were recorded daily to assess the degree of colitis inflammation. Expression levels of HSP90 and MAPK pathway-related genes and proteins were evaluated by Western blot and qPCR. The evaluation of intestinal mucosal permeability was measured by enzyme-linked immunosorbent assay (ELISA), which could detect the protein level of D-Amino Acid Oxidase (DAO) and D-lactic acid (D-LA). The same went for downstream molecules AFT-2, p53, and apoptosis-related proteins BAX, BCL-2, Caspase3, and survivin in the MAPK pathway. Immunohistochemical measured p-38, p-JNK, and p-ERK expressions. JAM-A and claudin-1 connexin were tested by immunofluorescence staining. The TUNEL method was for measuring the apoptosis rate of colonic epithelial cells. CBA kit determined the level of inflammatory factors of colons. Results: HSP90 inhibitor can improve the degree of pathological damage in the colon of mice treated with DSS, increase the mice's weight and the length of the colon, and significantly reduce the disease activity index (DAI) score. Intraperitoneal injection of HSP90 inhibitor can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation and decrease the content of AFT-2 and p53, which is downstream of the MAPK pathway. In addition, treatment of the HSP90 inhibitor up-regulated the expression of anti-apoptotic proteins BCL-2 and survivin, as well as down-regulated apoptotic protein caspase3, BAX in the colon of mice with colitis. Lower levels of inflammatory factors such as IL-6, MCP-1, IFN-γ, TNF, IL-12p70, and increased IL-10 were observed after HSP90 inhibitor therapy. Furthermore, the combination treatment of CSD can enhance the effect of the single HSP90 inhibitor treatment and play a synergistic effect. Conclusion: These data suggest that an HSP90 inhibitor is available to treat UC by inhibiting the MAPK signaling pathway. This axis can restore the intestinal mucosa barrier's function by reducing intestinal mucosa's permeability and inhibiting apoptosis of intestinal epithelial cells. The specific mechanism is that HSP90 inhibitor can reduce the pathological damage and inflammation levels of colitis mice, and reduce the apoptosis rate of colonic epithelial cells and the mucosal permeability, thereby restoring the mucosal barrier function. During this process, CSD works synergistically to improve the therapeutic effect of the HSP90 inhibitor.