Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity

Inhibition of bone resorption by Tanshinone VI isolated from Salvia miltiorrhiza Bunge

During the last decade, a more detailed knowledge of molecular mechanisms involved in osteoclastogenesis has driven research efforts in the development and screening of compound libraries of several small molecules that specifically inhibit the pathway involved in the commitment of the osteoclast precursor cells. Natural compounds that suppress osteoclast differentiation may have therapeutic value in treating osteoporosis and other bone erosive diseases such as rheumatoid arthritis or metastasis associated with bone loss. In ongoing investigation into anti-osteoporotic compounds from natural products we have analyzed the effect of Tanshinone VI on osteoclasts differentiation, using a physiologic three-dimensional osteoblast/bone marrow model of cell co-culture. Tanshinone VI is an abietane diterpene extracted from the root of Salvia miltiorrhiza Bunge (Labiatae), a Chinese traditional crude drug, “Tan-Shen”. Tashinone has been widely used in clinical practice for the prevention of cardiac diseases, arthritis and other inflammation-related disorders based on its pharmacological actions in multiple tissues. Although Tanshinone VI A has been used as a medicinal agent in the treatment of many diseases, its role in osteoclast-related bone diseases remains unknown. We showed previously that Tanshinone VI greatly inhibits osteoclast differentiation and suppresses bone resorption through disruption of the actin ring; subsequently, we intended to examine the precise inhibitory mechanism of Tanshinone VI on osteoclast differentiating factor. This study shows, for the first time, that Tanshinone VI prevents osteoclast differentiation by inhibiting RANKL expression and NFkB induction

PROTEOMICS AS USEFUL TOOL FOR STUDING BIOMARKERS OF EARLY EXPOSURE TO POLYCHLORINATED BIPHENILS

Polychlorinated biphenyls (PCBs) are toxic persistent organic pollutants present in the hydrosphere. Mussels are used as sentinel organisms for the monitoring of marine pollution for their ability to bioaccumulate contaminants, their sessile nature, filter-feeding habits and widespread distribution. Alteration in protein expression is often indicative of toxic exposure or effect and changes in protein expression profiles derived from environmental stress may be used for the identification of novel biomarkers. In this study, proteomics has been used in mussels as a preliminary screening of quantitative changes in protein expression caused by a mixture of PCBs, potentially useful as new biomarkers, following the identification of the proteins more drastically altered. Our data demonstrated that proteomic approach represents a valuable tool for identifying biomarkers of exposure to environmental contaminants

Proteomic approach for the detection of biomarkers ofexposure in mussels exposed to PCB

In the current study, a preliminary proteomic approach has been used in Mytilus galloprovincialis as a screening of changes in protein expression caused by a mixture of polychlorinated biphenyls (PCBs), in order to characterize the effects of PCBs on the protein profile and to develop new molecular biomarkers, after identifying the proteins more drastically altered. Methods:Mussels were exposed for three weeks to three polychlorinated biphenyls under controlled conditions. The edible parts were homogenized and lyophilized. Extracted proteins were quantified and separated by two-dimensional electrophoresis (2-DE) in IPG strips (pH 3–10). The protein spots in gels were visualized by Coomassie Brilliant Blue staining. Gel images were obtained using a Image Scanner. Image analysis included spot detection, quantification and matching. The volume of each spot from each gel was normalized to the total gel spot volume in order to correct it for differences in gel staining. More than 500 spots were resolved and altered expression was qualitatively detected. Results and conclusions of the study: Our results showed a well conserved protein pattern regardless of the treatments, demonstrating that the exposition to the PCB mixture did not impair the normal physiological function of the mussels. However, the levels of a restricted number of proteins were clearly and reproducibly affected by the treatment; therefore, these polypeptides were considered promising biomarker candidates. In conclusion, even if further studies are needed to validate these findings, our data demonstrated that proteomic approach represents a valuable tool for identifying biomarkers of exposure to environmental contaminants

Multipoint temperature monitoring of microwave thermal ablation in bones through fiber bragg grating sensor arrays

Bones are a frequent site of metastases that cause intolerable cancer-related pain in 90% of patients, making their quality of life poor. In this scenario, being able to treat bone oncology patients by means of minimally invasive techniques can be crucial to avoid surgery-related risks and decrease hospitalization times. The use of microwave ablation (MWA) is gaining broad clinical acceptance to treat bone tumors. It is worth investigating temperature variations in bone tissue undergoing MWA because the clinical outcomes can be inferred from this parameter. Several feasibility studies have been performed, but an experimental analysis of the temperature trends reached into the bone during the MWA has not yet been assessed. In this work, a multi-point temperature study along the bone structure during such treatment is presented. The study has been carried out on ex vivo bovine femur and tibia, subjected to MWA. An overall of 40 measurement points covering a large sensing area was obtained for each configuration. Temperature monitoring was performed by using 40 fiber Bragg grating (FBGs) sensors (four arrays each housing 10 FBGs), inserted into the bones at specific distances to the microwave antenna. As result, the ability of this experimental multi-point monitoring approach in tracking temperature variations within bone tissue during MWA treatments was shown. This study lays the foundations for the design of a novel approach to study the effects of MWA on bone tumors. As consequence, the MWA treatment settings could be optimized in order to maximize the treatment effects of such a promising clinical application, but also customized for the specific tumor and patient

Impact of ploidy change on secondary metabolites and photochemical efficiency in Solanum bulbocastanum Dun.

Plants are well known for producing a wide diversity of natural compounds and several strategies have been proposed to enhance their production. Among them, somatic chromosome doubling may represent an effective and inexpensive method. The objective of the current study was to investigate the effect of polyploidization on the leaf metabolic profile and content of tetraploids produced from a wild diploid (2n=2x=24) potato species, Solanum bulbocastanum Dun. Photochemical efficiency of tetraploids was also analyzed. Results from HPLC-DAD and LC/MS analyses provided evidence that tetraploid genotypes displayed either a similar or a lower phenylpropanoids, tryptophan, tyrosine and α-chaconine content compared with the diploid parent. Similarly, no significant differences were found among genotypes both for measures of gas and for chlorophyll fluorescence, except for non-photochemical quenching (NPQ). Steroidal saponins content revealed superiority of some tetraploids with respect to the diploid parent, suggesting perturbations in the mechanism regulating the biosynthesis of such compounds following polyploidization. Lack of superiority may be attributed to the time required for adjustment, adaptation and evolution after the genomic shock induced by polyploidization, as well as the fact that an optimum ploidy level for each species may be crucial. Our results suggest that polyploidization as a strategy to enhance metabolite production cannot be generalized

Secondary metabolite profile in induced tetraploids of wild Solanum commersonii Dun.

The main aim of this work was to study the leaf secondary metabolite profiles of artificially induced tetraploids (2n1⁄44x1⁄448) of Solanum commersonii, a diploid (2n1⁄42x1⁄424) wild potato species. The tetraploid genotypes of S. commersonii were produced by oryzalin treatment. Both HPLC-UV and LC/ MS analyses revealed that there were no qualitative differences in the metabolite profiles between the diploid S. commersonii and its tetraploids. By contrast, the results showed that the phenylpropanoid content was generally significantly higher in the tetraploids than in the diploid S. commersonii. Concerning the glycoalkaloids (GAs), the results provided evidence that the content of minor GAs (solanidenediol triose, solanidadienol lycotetraose, and solanidenol lycotetraose) was higher in tetraploids than in the diploid progenitor, while the content of major GAs (dehydrodemissine and dehydrocommersonine) was significantly higher in diploid S. commersonii than in its tetraploid genotypes. The results are discussed from the practical perspective of potato biodiversity enhancement

Impact of ploidy change on secondary metabolites and photochemical efficiency in Solanum bulbocastanum Dun.

Plants are well known for producing a wide diversity of natural compounds and several strategies have been proposed to enhance their production. Among them, somatic chromosome doubling may represent an effective and inexpensive method. The objective of the current study was to investigate the effect of polyploidization on the leaf metabolic profile and content of tetraploids produced from a wild diploid (2n=2x=24) potato species, Solanum bulbocastanum Dun. Photochemical efficiency of tetraploids was also analyzed. Results from HPLC-DAD and LC/MS analyses provided evidence that tetraploid genotypes displayed either a similar or a lower phenylpropanoids, tryptophan, tyrosine and α-chaconine content compared with the diploid parent. Similarly, no significant differences were found among genotypes both for measures of gas and for chlorophyll fluorescence, except for non-photochemical quenching (NPQ). Steroidal saponins content revealed superiority of some tetraploids with respect to the diploid parent, suggesting perturbations in the mechanism regulating the biosynthesis of such compounds following polyploidization. Lack of superiority may be attributed to the time required for adjustment, adaptation and evolution after the genomic shock induced by polyploidization, as well as the fact that an optimum ploidy level for each species may be crucial. Our results suggest that polyploidization as a strategy to enhance metabolite production cannot be generalized

Bioactive Limonoids from the Leaves of Azaridachta indica (Neem)

Eight new limonoids (1−8) and one new phenol glycoside (9), along with six known compounds, were isolated from the leaves of Azaridachta indica. The structures of 1−9 were elucidated on the basis of spectroscopic data analysis. Compounds isolated were assayed for their cytotoxicity against different cancer cell lines. Moreover, their ability to interact with the molecular chaperone Hsp90, affecting its biological activity, was tested