Preclinical assessment of MAGMAS inhibitor as a potential therapy for pediatric medulloblastoma.

Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and non-SHH group3 subtypes. MAGMAS (Mitochondrial Associated Granulocyte Macrophage colony-stimulating factor Signaling molecules) encode for mitochondrial import inner membrane translocase subunit and is responsible for translocation of matrix proteins across the inner membrane. We previously reported that a small molecule MAGMAS inhibitor, BT9, decreases cell proliferation, migration, and oxidative phosphorylation in adult glioblastoma cell lines. The aim of our study was to investigate whether the chemotherapeutic effect of BT9 can be extended to pediatric medulloblastoma. Methods: Multiple in vitro assays were performed using human DAOY (SHH activated tp53 mutant) and D425 (non-SHH group 3) cells. The impact of BT9 on cellular growth, death, migration, invasion, and metabolic activity were quantified using MTT assay, TUNEL staining, scratch wound assay, Matrigel invasion chambers, and seahorse assay, respectively. Survival following 50mg/kg BT9 treatment was assessed in vivo in immunodeficient mice intracranially implanted with D425 cells. Results: Compared to control, BT9 treatment led to a significant reduction in medulloblastoma cell growth (DAOY, 24hrs IC50: 3.6uM, 48hrs IC50: 2.3uM, 72hrs IC50: 2.1uM; D425 24hrs IC50: 3.4uM, 48hrs IC50: 2.2uM, 72hrs IC50: 2.1uM) and a significant increase in cell death (DAOY, 24hrs p=0.0004, 48hrs p<0.0001; D425, 24hrs p=0.0001, 48hrs p=0.02). In DAOY cells, 3uM BT9 delayed migration, and significantly decreased DAOY and D425 cells invasion (p < 0.0001). Our in vivo study, however, did not extend survival in xenograft mouse model of group3 medulloblastoma compared to vehicle-treated controls. Conclusions: Our in vitro data showed BT9 antitumor efficacy in DAOY and D425 cell lines suggesting that BT9 may represent a promising targeted therapeutic in pediatric medulloblastoma. These data, however, need to be further validated in animal models.

Dual targeting of mitochondrial Lon peptidase 1 and chymotrypsin-like protease by small molecule BT317, as potential therapeutics in malignant astrocytoma.

Malignant astrocytomas are aggressive glioma tumors characterized by extensive hypoxia-induced, mito-chondria-dependent changes such as altered respiration, increased chymotrypsin-like (CT-L) proteasome activity, decreased apoptosis, drug resistance, stemness and increased invasiveness. Mitochondrial Lon Peptidase I (LonP1) overexpression and increased CT-L proteasome inhibitors activity are the biomarkers of aggressive high grade glioma phenotype, poor prognosis and found to be associated with recurrence and poor patient survival, and drugs targeting either LonP1 or the CT-L activity have anti-glioma activity in pre-clinical models. We here for the first time introduced and evaluated a novel small molecule, BT317, derived from coumarinic compound 4 (CC4) using structure-activity modeling which we found to inhibit both LonP1 and CT-L proteasome activity. Using gain-of-function and loss-of-function genetic models, we dis-covered that BT317 is more effective than the individual LonP1 or CT-L inhibition in increasing reactive oxy-gen species (ROS) generation and inducing apoptosis in high-grade astrocytoma lines. In vitro, BT317 had activity as a single agent but, more importantly, enhanced synergy with the standard of care commonly used chemotherapeutic temozolomide (TMZ). In orthotopic xenograft, patient derived glioma models, BT317 was able to cross the blood-brain barrier, to show selective activity at the tumor site and to demonstrate therapeutic efficacy both as a single agent and in combination with TMZ. BT317 defines an emerging class of dual LonP1, and CT-L proteasome inhibitors exhibited promising anti-tumor activity and could be a promising candidate for clinical translation in the space of malignant astrocytoma therapeutics.

HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.

Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.

Identification of new hit to lead magmas inhibitors as potential therapeutics for glioblastoma.

In continuation of our previous efforts for the development of potent small molecules against brain cancer, herein we synthesized seventeen new compounds and tested their anti-gliomapotential against established glioblastoma cell lines, namely, D54MG, U251, and LN-229 as well as patient derived cell lines (DB70 and DB93). Among them, the carboxamide derivatives, BT-851 and BT-892 were found to be the most active leads in comparison to our established hit compound BT#9.The SAR studies of our hit BT#9 compound resulted in the development of two new lead compounds by hit to lead strategy. The detailed biological studies are currently underway. The active compounds could possibly act as template for the future development of newer anti-glioma agents.

Anti-inflammatory Action of BT75, a Novel RARα Agonist, in Cultured Microglia and in an Experimental Mouse Model of Alzheimer's Disease.

BT75, a boron-containing retinoid, is a novel retinoic acid receptor (RAR)α agonist synthesized by our group. Previous studies indicated that activation of retinoic acid (RA) signaling may attenuate progression of Alzheimer's disease (AD). Presently, we aimed to examine the anti-inflammatory effect of BT75 and explore the possible mechanism using cultured cells and an AD mouse model. Pretreatment with BT75 (1-25 µM) suppressed the release of nitric oxide (NO) and IL-1ß in the culture medium of mouse microglial SIM-A9 cells activated by LPS. BMS195614, an RARα antagonist, partially blocked the inhibition of NO production by BT75. Moreover, BT75 attenuated phospho-Akt and phospho-NF-κB p65 expression augmented by LPS. In addition, BT75 elevated arginase 1, IL-10, and CD206, and inhibited inducible nitric oxide synthase (iNOS) and IL-6 formation in LPS-treated SIM-A9 cells, suggesting the promotion of M1-M2 microglial phenotypic polarization. C57BL/6 mice were injected intracerebroventricularly (icv) with streptozotocin (STZ) (3 mg/kg) to provide an AD-like mouse model. BT75 (5 mg/kg) or the vehicle was intraperitoneally (ip) injected to icv-STZ mice once a day for 3 weeks. Immunohistochemical analyses indicated that GFAP-positive cells and rod or amoeboid-like Iba1-positive cells, which increased in the hippocampal fimbria of icv-STZ mice, were reduced by BT75 treatment. Western blot results showed that BT75 decreased levels of neuronal nitric oxide synthase (nNOS), GFAP, and phosphorylated Tau, and increased levels of synaptophysin in the hippocampus of icv-STZ mice. BT75 may attenuate neuroinflammation by affecting the Akt/NF-κB pathway and microglial M1-M2 polarization in LPS-stimulated SIM-A9 cells. BT75 also reduced AD-like pathology including glial activation in the icv-STZ mice. Thus, BT75 may be a promising anti-inflammatory and neuroprotective agent worthy of further AD studies.

New Boron Delivery Agents.

This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on April 20-22, 2022. The most used boron sources are icosahedral boron clusters attached to peptides, proteins (such as albumin), porphyrin derivatives, dendrimers, polymers, and nanoparticles, or encapsulated into liposomes. These boron clusters and/or carriers can be labeled with contrast agents allowing for the use of imaging techniques, such as PET, SPECT, and fluorescence, that enable quantification of tumor-localized boron and their use as theranostic agents.

Quantification of cucurbitacin E in different varieties of melon (Cucumis melo L.) fruit through validated RP-HPLC method.

The different varieties of melons (Cucumis melo L.) have been used in various traditional systems of medicine for decades to treat different ailments, including inflammation, cancer, cardiovascular, diabetes, edema, etc. The present study was designed for the quantification of cucurbitacin E in five different varieties of melon fruit through a validated RP-HPLC method. A solvent system is being optimized with a 70:30 (v/v) ratio of acetonitrile: water (1% glacial acetic acid) at a 1 mL/min flow rate and scanning spectrum (λmax) of 230 nm. A calibration curve for standard cucurbitacin E was generated and found to be linear (1-100 µg/mL). The variation of cucurbitacin E content among five different varieties of melon fruits is 0.0129% w/w- 0.231% w/w. This precise and reproducible method may be beneficial in addressing the quality-related aspects of medicinal food plants of Cucurbitaceae and its derived products or formulations.

Magmas Inhibition in Prostate Cancer: A Novel Target for Treatment-Resistant Disease.

The purpose of our study was to evaluate Magmas as a potential target in prostate cancer. In addition, we evaluated our synthetic Magmas inhibitor (BT#9) effects on prostate cancer and examined the molecular mechanism of BT#9. A cell viability assay showed that treatment with BT#9 caused a significant decrease in the viability of DU145 and PC3 prostate cancer cells with little effect on the viability of WPMY-1 normal prostate cells. Western blot proved that BT#9 downregulated the Magmas protein and caspase-3 activation. Flow cytometry studies demonstrated increased apoptosis and disturbed mitochondrial membrane potential. However, the main mode of cell death was caspase-independent necrosis, which was correlated with the accumulation of mitochondrial and intra-cellular Reactive Oxygen Species (ROS). Taken together, our data suggest Magmas is a potential molecular target for the treatment of prostate cancer and that Magmas inhibition results in ROS-dependent and caspase-independent necrotic cell death.

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure-activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer's agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Evaluation of Mollugo oppositifolia Linn. as cholinesterase and ß-secretase enzymes inhibitor.

Mollugo oppositifolia Linn. is traditionally used in neurological complications. The study aimed to investigate in-vitro neuroprotective effect of the plant extracts through testing against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-secretase linked to Alzheimer's disease (AD). To understand the safety aspects, the extracts were tested for CYP450 isozymes and human hepatocellular carcinoma cell (HepG2) inhibitory potential. The heavy metal contents were estimated using atomic absorption spectroscopy (AAS). Further, the antioxidant capacities as well as total phenolic content and total flavonoid content (TFC) were measured spectrophotometrically. UPLC-QTOF-MS/MS analysis was employed to identify phytometabolites present in the extract. The interactions of the ligands with the target proteins (AChE, BChE, and BACE-1) were studied using AutoDockTools 1.5.6. The results showed that M. oppositifolia extract has more selectivity towards BChE (IC50 = 278.23 ± 1.89 µg/ml) as compared to AChE (IC50 = 322.87 ± 2.05 µg/ml). The IC50 value against ß-secretase was 173.93 µg/ml. The extract showed a CC50 value of 965.45 ± 3.07 µg/ml against HepG2 cells and the AAS analysis showed traces of lead 0.02 ± 0.001 which was found to be within the WHO prescribed limits. Moreover, the IC50 values against CYP3A4 (477.03 ± 2.01 µg/ml) and CYP2D6 (249.65 ± 2.46 µg/ml) isozymes justify the safety aspects of the extract. The in silico molecular docking analysis of the target enzymes showed that the compound menthoside was found to be the most stable and showed a good docking score among all the identified metabolites. Keeping in mind the multi-targeted drug approach, the present findings suggested that M. oppositifolia extract have anti-Alzheimer's potential.

AMPK mediates regulation of glomerular volume and podocyte survival.

Herein, we report that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without focal segmental glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease (MCD), where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral and 5/6th nephrectomy models in Shroom3-KD mice. Knockdown mice exhibited less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying that Fyn was downstream of Shroom3. Using SHROOM3 or FYN knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMPK, a negative regulator of anabolism. AMPK activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMPK abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMPK activation. In agreement with this, treatment of glomerular injury models with AMPK activators restricted glomerular volume, podocytopenia, and progression to FSGS. Glomerular transcriptomes from MCD biopsies also showed significant enrichment of Fyn inactivation and Ampk activation versus FSGS glomeruli. In summary, we demonstrated the important role of AMPK in glomerular volume regulation and podocyte survival. Our data suggest that AMPK activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.

Increase in Cancer Patient Load during COVID-19 Pandemic: The Faridabad Experience.

Introduction Coronavirus disease 2019 (COVID-19) has affected oncology care differently across the world. We evaluated our experience of infusional chemotherapy during the active phase of ongoing pandemic. Methods Prospectively collected month wise data from January 2019 to November 2020 was compared between the 2 years. Results A total of 6,003 chemotherapy infusions were administered between January 1, 2019 and November 30, 2020 (2,548 in 11 months of 2019 and 3,455 in the same 11 months of 2020). Between May 1 and October 31, 2020, 2,337 chemotherapy infusions were administered to 570 patients all of whom were also tested for COVID-19 positivity, of which 65 (11.4%) were COVID-19 positive. The majority (63/65; 97%) could receive their chemotherapy infusions safely. Discussion Paradoxically, our hospital recorded an increase in the number of cancer patients receiving infusional chemotherapy in 2020, with a linear increase in the cancer case being treated (from 309 in June to 398 in November 2020). We believe that this was possible because cancer patients wanted treatment near their homes to avoid/minimize risk of exposure to COVID-19, cross state border travel restrictions was an additional roadblock, and our quality of service provided earned the trust of cancer patients.

Withania somnifera (L.) Dunal - Modern perspectives of an ancient Rasayana from Ayurveda.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for more than 3000 years. According to Charaka Samhita, Susruta Samhita and other ancient texts, Ashwagandha is known as Balya (increases strength), Brusya (sexual performance enhancer), vajikari (spermatogenic), Kamarupini (libido-enhancing), Pustida (nourishing). AIM OF THE REVIEW: This review article documented and critically assessed W. somnifera regarding its ethnopharmacology, traditional use, botanical description, phytochemicals present, pharmacological activities, clinical trials, and marketed formulations. MATERIALS AND METHODS: The sources of information used in the study are traditional Ayurvedic books like Charaka Samhita, Susruta Samhita, Astanga Hridaya etc, government reports, dissertations, books, research articles and databases like Science-Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, and ACS Publications on Ashwagandha and Withania somnifera (L.) Dunal. RESULTS: Traditional uses of Ashwagandha in Ayurveda are very prominent in several texts where formulations with various dosage forms have been mentioned in Charaka Samhita, Susruta Samhita, Astanga Hridaya, different nighantus etc. The drugs were identified based on their composition containing Ashwagandha as one of the major ingredients and their medicinal uses. Phytochemical studies on W. somnifera revealed the presence of important chemical constituents such as flavonoids, phenolic acids, alkaloids, saponins, tannins, and withanolides. The phytochemicals showed various pharmacological activities like anti-cancer, immunomodulatory, cardioprotective, neuroprotective, anti-aging, anti-stress/adaptogenic and anti-diabetic. Various clinical trials show that the plant extract and its bioactive compounds are used in the prevention and treatment of many diseases, such as arthritis, impotence, amnesia, anxiety, cancer, neurodegenerative and cardiovascular diseases, and others. CONCLUSIONS: Pharmacological data reviewed here revealed that W. somnifera is a potential source for the treatment of a wide range of diseases especially anxiety and other CNS disorders. From its ancient use to its modern application it has been proven to be non-toxic and effective clinically for human health and wellness. W. somnifera based herbal formulation has been marketed in the form of supplement, extract, capsule, powder etc. This review will be helpful to correlate the mechanism of action with the phytochemical profile of this well-known plant from Ayurveda.

BF175 inhibits endometrial carcinoma through SREBP-regulated metabolic pathways in vitro.

Elevated lipogenesis is an important metabolic hallmark of rapidly proliferating tumor such as endometrial carcinoma (EC). The sterol regulatory element-binding protein 1 (SREBP1) is a master regulator of lipogenesis and involved in EC proliferation. BF175 is a novel chemical inhibitor of SREBP pathway, and has shown potent anti-lipogenic effects. However, the effect of BF175 on EC cells are yet to be determined. In the present study, we found that BF175 decreased cell viability, colony formation and migratory capacity, inducing autophagy and mitochondrial related apoptosis in EC cell line AN3CA. Z-VAD-FMK partially attenuated the effect of BF175 on AN3CA. In addition, BF175 significantly downregulated SREBPs and their downstream genes. The levels of free fatty acids and total cholesterol were also inhibited. Microarray analysis suggested BF175 treatment obviously affected lipid metabolic pathways in EC. Taken together, we validated BF175 exhibited anti-tumor activity by targeting SREBP-dependent lipogenesis and inducing apoptosis which mitochondrial pathway involved in, suggesting that it's potential as a novel therapeutic reagent for EC.

Characterization of an arabinogalactan isolated from gum exudate of Odina wodier Roxb.: Rheology, AFM, Raman and CD spectroscopy.

Purified gum odina (PGO) from Odina wodier Roxb. was characterized by rheology, AFM, Raman and CD spectroscopy, in vitro antioxidant activity against hydroxyl radical and superoxide radical, and total antioxidant capacity. The PGO dispersions exhibited pseudoplastic behaviour. The viscosity of dispersion increased with increasing PGO concentration, but decreased with increasing temperature and added salt concentration. The loss modulus was higher than storage modulus indicating prevalently viscous characteristics. AFM analysis showed irregular spherical lumps due to inter- and intramolecular interactions. The Raman spectrum of PGO was similar to that of gum arabic. Circular dichroism revealed partial adoption of polyproline II type conformation, suggesting a less compact structure. The PGO was found to scavenge hydroxyl radical (IC50 517.68 ± 3.60 µg/mL) and superoxide radical (IC50 586.21 ± 3.41 µg/mL), and possess total antioxidant capacity (9.64 ± 0.23 mg gallic acid equivalent/g). Overall, this work would exploit PGO as a new hydrocolloid source in the food and pharmaceutical industries.

Role of SIRT1 in HIV-associated kidney disease.

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.

Scaffold-based Screening and Molecular Dynamics Simulation Study to Identify Two Structurally Related Phenolic Compounds as Potent MMP1 Inhibitors.

BACKGROUND: Matrix metalloproteinase 1 are zinc-dependent endopeptidases responsible for the controlled breakdown of the extracellular matrix resulting in the maintenance of homeostasis. Dysregulation of MMP1 leads to the progression of various pathological conditions like cancer, rheumatoid arthritis, cardiovascular disease, skin damage and fibrotic disorder. Thus, MMP1 inhibition is the potential drug target of many synthetic MMP1 inhibitors but lack of substrate specificity hinders their clinical applicability. Hence, inhibitors from natural products have gained widespread attention. OBJECTIVE: The present study attempts screening of novel MMP1 inhibitors from the ZINC database based on experimentally reported natural inhibitors of MMP1 as a scaffold. METHODS: Molecular docking study was performed with 19 experimentally reported natural inhibitors spanning across nine different classes followed by virtual screening using the selected compounds. The selected compounds were subjected to molecular dynamics simulation. RESULTS: Twenty compounds were screened with a cut-off of -9.0 kcal/mol of predicted free energy of binding, which further converged to 6 hits after docking studies. After comparing the docking result of 6 screened hits, two best compounds were selected. ZINC02436922 had the best interaction with six hydrogen bond formation to a relatively confined region in the S1'site of MMP1 and -10.01 kcal/mol of predicted free energy of binding. ZINC03075557 was the secondbest compound with -9.57 kcal/mol predicted binding free energy. Molecular dynamics simulation of ZINC02436922 and ZINC03075557 corroborates docking study. CONCLUSION: This study indicated phenolic compounds ZINC02436922 and ZINC03075557 as potential MMP1 inhibitors.

Metabolite profiling and in-vitro colon cancer protective activity of Cycas revoluta cone extract.

The methanolic extract of Cycas revoluta cone (MECR) was analyzed by GC-MS and UHPLC for metabolite profiling and was evaluated for anti-colon cancer property by using in vitro assays like Cell Viability Assay, Colony Formation Assay, ROS Determination, Flowcytometry, DAPI staining assay, Tunel assay. GC-MS and HPLC analysis confirmed the presence of different phytochemicals in the extract of Cycas revoluta cone. In-vitro studies showed MECR extract showed significant anti-colon cancer activity by reducing proliferation and inducing apoptosis in colon cancer cell (HCT-8) line, but no such activity was seen in normal colon cell (CCD-18Co) line. The investigation confirms that MECR may be a promising candidate in colon cancer protection.

A cost-effective and environmentally sustainable process for phycoremediation of oil field formation water for its safe disposal and reuse.

High volumes of formation water comprising of complex mixture of hydrocarbons is generated during crude oil exploration. Owing to ecotoxicological concerns, the discharge of the formation water without remediation of hydrocarbonaceous pollutants is not permitted. Keeping this into mind, we carried out phycoremediation of hydrocarbons in formation water so that it can be safely discharged or re-used. For this, a native algal species was isolated from formation water followed by its morphological and 18S ribosomal RNA based identification confirming the algal isolate to be Chlorella vulgaris BS1 (NCBI GenBank Accession No. MH732950). The algal isolate exhibited high biomass productivity of 1.76 gm L-1 d-1 (specific growth rate: 0.21 d-1, initial inoculum: 1500 mg L-1) along with remediation of 98.63% petroleum hydrocarbons present in formation water within 14 days of incubation indicating an efficient hydrocarbon remediation process. Concomitantly, the hydrocarbon remediation process resulted in reduction of 75% Chemical Oxygen Demand (COD) load and complete removal of sulfate from formation water making it suitable for safe disposal or reuse as oil well injection water respectively. The present process overcomes the bottlenecks of external growth nutrient addition or dilution associated with conventional biological treatment resulting in a practically applicable and cost-effective technology for remediation of oil field formation water.

SMARC-B1 deficient sinonasal carcinoma metastasis to the brain with next generation sequencing data: a case report of perineural invasion progressing to leptomeningeal invasion.

BACKGROUND: SMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread. CASE PRESENTATION: A 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary. CONCLUSIONS: This is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors.