Hydro-uvarovite from Mantle Peridotites of Naga Hills Ophiolite: A Mineral Tracer for Neo-Tethyan Mantle Wedge Metasomatism

Hydrous Cr-bearing uvarovite garnets are rare in natural occurrences and belong to the ugrandite series and exist in binary solid solutions with grossular and andradite garnets. Here, we report the occurrence of hydrous uvarovite garnet having Cr_(2)O_(3) upto 19.66 wt% and CaO of 32.12–35.14 wt% in the serpentinized mantle peridotites of Naga Hills Ophiolite(NHO), India. They occur in association with low-Cr diopsides. They are enriched in LILE(Ba, Sr), LREEs, with fractionating LREE-MREE [avg.(La/Sm)_(N) = 2.16] with flat MREE/HREE patterns [avg.(Sm/Yb)_(N) = 0.95]. Raman spectra indicate the presence of hydroxyl(OH^(–)) peaks from 3500 to 3700 cm^(-1). Relative abundances in fluid mobile elements and their close association with clinopyroxenes are suggestive of the formation of uvarovite garnets through low temperature metasomatic alteration of low-Cr diopsides by hydrothermal slab fluids. The high LREE concentration and absence of Eu anomaly in the garnet further attest to alkaline nature of the transporting slab dehydrated fluid rather the involvement of low-p H solution. The chemical characteristics of the hydroxyl bearing uvarovite hosted by the mantle peridotite of NHO deviate from the classical features of uvarovite garnet, and their origin is attributed to the fluid-induced metasomatism of the sub arc mantle wedge in a suprasubduction zone regime.

Bulbine frutescens phytochemicals as novel ABC-transporter inhibitor:a molecular docking and molecular dynamics simulation study

Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.

Resistance to second generation antiandrogens in prostate cancer: pathways and mechanisms

Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling pathways.In this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC emergence.Evolving knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.