TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells.

The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the formation of TERRA-LSD1 condensates enriches the R-loop stimulating protein Rad51AP1 and increases TERRA-containing R-loops at telomeres. Our findings suggest that LSD1-TERRA phase separation enhances the function of R-loop regulatory molecules for ALT telomere maintenance, providing a mechanism for how the biophysical properties of histone modification enzyme-RNA interactions impact chromatin function.

Communication About Chimeric Antigen Receptor T-Cell (CAR-T) Therapy.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of patients with hematologic malignancies, yet treatment may coincide with the potential for life-threatening toxicities. Currently, no studies have investigated how oncologists communicate with patients about CAR-T therapy or what patients and their caregivers want to know prior to consenting for CAR-T therapy. This study characterizes the content of oncologist communication with patients and caregivers about the risks and benefits of CAR-T therapy and explore the information preferences of patients and their caregivers about CAR-T therapy. We conducted a multimethod study of 20 patients with hematologic malignancies referred for CAR-T therapy at the Massachusetts General Hospital and 10 caregivers. We audio recorded the initial outpatient visit with the oncologist to review and sign consent for CAR-T therapy. We subsequently surveyed patients and caregivers about information gaps that remained after consent. We then interviewed patients and caregiver about their perceptions of oncologist communication and information preferences after the consent visit, 1 month, and 3 months post-CAR-T therapy treatment. Qualitative data analysis was conducted using the framework approach. Six major themes regarding communication about CAR-T therapy were identified: (1) oncologists create a narrative of power and innovation about CAR-T therapy, (2) oncologists set clear expectations regarding CAR-T therapy, (3) oncologists preferentially discuss positive treatment outcomes and less frequently address treatment failures or uncertainties, (4) oncologists couple their discussion about risks of CAR-T therapy with assurances about risk mitigation strategies, (5) oncologists engage in empathetic communication throughout the consent visit, (6) patients and caregivers vary in their preferences regarding communication about CAR-T therapy but largely favor a positive discourse during the consent visit and (7) patients who completed CAR-T therapy and their caregivers report significant knowledge gaps during and after treatment. Overall, patients and caregivers felt well informed about CAR T-therapy yet identified communication gaps regarding, advanced care planning, treatment failure and treatment toxicities. A predominantly positive discourse between patients, caregivers, and oncologists around CAR-T therapy leaves patients and caregivers with significant knowledge gaps about negative outcomes. Further research is needed to help oncologists communicate about treatment uncertainties and help patients and their caregivers prepare for negative outcomes of CAR-T therapy.

A comparative study of antimicrobial and anti-inflammatory efficiency of modified solvent evaporated and vacuum oven dried bioactive components of Pleurotus floridanus.

In the present study, we compared vacuum microwave oven drying Vacuum Oven Drying (VOD) and modified solvent evaporation (MSE) assisted methanolic mushroom extracts for their antimicrobial and anti-inflammatory efficacy. MSE extract showed significantly (p < 0.05) higher total phenolic content (64.4 mg/g) followed by flavonoid content (20.62 mg/g), ascorbic acid (17.54 mg/g), ß-carotene content (12.52 mg/g), and lycopene (9.57 mg/g) content than that of VOD extract. MSE showed a significantly (p < 0.05) higher zone of inhibition against all selected microorganisms as compared to VOD extract. During the time-kill study, the MSE extract inhibited significantly (p < 0.05) higher growth of Staphylococcus aureus followed by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli than that of VOD extract. Also, MSE extract showed significantly (p < 0.05) higher anti-inflammatory activity in comparison with VOD extract during the Human Red Blood Cell (HRBC) membrane stabilization test and albumin denaturation test. MSE extract revealed significantly (p < 0.05) higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N2O2 scavenging assay than that of VOD extract, however, statistically, MSE extract showed comparable results with Butylated Hydroxyanisole (BHA) and Butylated Hydroxytoluene (BHT). During the characterization of the selected extract, Fourier transform infrared spectroscopy confirmed the functional groups of the flavonoid content, ascorbic acid, ß-carotene, and lycopene. Quantitative analysis of gallic acid (54.32 mg/g) and rutin content (14.80 mg/g) was revealed using a high-pressure liquid chromatogram.

Biological activities of Pleurotus spp. polysaccharides: A review.

Mushrooms are consumed for their nutrients and therapeutic bioactive compounds and are used medicinally in Chinese and Japanese medicine traditions since time immemorial. Members of the genus Pleurotus form a heterogeneous group of edible species with outstanding nutritional profiles rich in fiber, vitamins (thiamine, riboflavin, ascorbic acid, ergosterine, and niacin), micro and macro-elements (phosphorus and iron), and carbohydrates. Pleurotus is one of the most diversified medicinal and edible mushrooms related to the composition of chemical structures such as polysaccharides, glycoproteins, and secondary metabolites such as alkaloids and betalains. The cultivation of Pleurotus spp. on lignocellulosic wastes represents one of the most economically and cost-effective organic recycling processes, especially for the utilization of different feasible and cheap recyclable residues. Also, several Pleurotus spp. have the ability to remove phenolic compounds from wastewater with the action of phenoloxidase activity. Here, we have reviewed the chemistry of such polysaccharides and their reported biological activities, namely, anti-inflammatory, immunomodulatory, anti-diabetic, anti-tumor, antioxidant, etc. The mechanism of action and effects of novel polysaccharides extracted from various species of Pleurotus have been studied. The current study will be beneficial for guiding future research projects on the above concept and investigating more deeply the health of human beings. PRACTICAL APPLICATIONS: Mushrooms are one of the most delicious foods around the globe and have many medicinal properties for decades. Various Pleurotus species have been in focus in recent years because of their palatability and medicinal importance too. It contains many bioactive compounds among which polysaccharides are valued to a great extent. Many biological activities are exerted by polysaccharides derived from the Pleurotus spp., namely, anti-tumor, antioxidant, and many more. They are responsible for significant physiological responses in animals, animal-alternative in vitro models, and humans. Their important physicochemical characteristics benefit their use in the food industry as well. So, the biological activities of these Pleurotus spp. polysaccharides will provide an insight to develop Pleurotus spp. as functional foods, because of their nutritional value and presence of bioactive components.

Synchronous primary cancers of urinary bladder and kidney and prostate.

Synchronous occurrence of two or more than two primary cancers of the urinary tract is quite rare, and poses a difficult treatment challenge. Here, we present a case of synchronous renal cell carcinoma, transitional cell carcinoma of urinary bladder and adenocarcinoma of prostate diagnosed within a short period. To the best of our knowledge, this is the first case reported from India and the youngest patient reported in the literature having this combination of urinary cancers.

Extracellular Ligninolytic Enzymes in Bjerkandera adusta and Lentinus squarrosulus.

Extracellular ligninolytic enzyme activities were determined in two white-rot fungi, Bjerkandera adusta and Lentinus squarrosulus. To investigate the activity of extracellular enzymes, cultures were incubated over a period of 20 days in nutrient rich medium (NRM) and nutrient poor medium under static and shaking conditions. Enzymatic activity was varied with media and their incubation conditions. The highest level of Aryl alcohol oxidase (AAO) was detected under shaking condition of both medium while Manganese peroxidase (MnP) activity was best in NRM under both conditions. AAO is the main oxidases enzyme in B. adusta while laccase plays important role in L. squarrosulus. MnP is the main peroxidase enzyme in both varieties.

Mineralization of mono-nitrophenols by Bjerkandera adusta and Lentinus squarrosulus and their extracellular ligninolytic enzymes.

Nitroaromatic compounds constitute a major class of widely distributed environmental contaminants. Fifty fungal strains were screened for their potential to tolerance with 2-nitrophenol, 3-nitrophenol and 4-nitrophenol on solid medium supplemented with 2% malt extract (MEA). Growth rate (mm/day) was determined at three concentrations (0.25, 0.5 and 1 mM) of all the three nitrophenols. From the fifty fungal strains only Bjerkandera adusta and Lentinus squarrosulus were able to tolerate all the three nitrophenols (NPs). These white-rot fungi (WRF) were chosen for liquid medium studies for the mineralization of mono-nitrophenols and ligninolytic enzyme activity at 0.25 mM concentration. Both varieties completely removed 2-NP and 3-NP while 4-NP was hard to mineralize. AAO (Aryl Alcohol Oxidase) is the main oxidase enzyme in B. adusta while laccase plays important role in L. squarrosulus. MnP (Manganese peroxidase) is the main peroxidase enzyme in both varieties. These fungal strains were capable to degrade nitrophenols and could be used for bioremediation applications on large scale.

Prostatic abscess: diagnosis and management in the modern antibiotic era.

This retrospective study was aimed at analyzing the clinical findings and therapeutic strategies in 24 patients who were admitted with prostatic abscess, during the period from 1999 to 2008. The diagnosis of prostatic abscesses was made clinically by digital rectal palpation based on the presence of positive fluctuation with tenderness. All cases were confirmed by trans-rectal ultrasound (TRUS), and only positive cases were included in this study. The diagnostic work-up included analysis of midstream urine and abscess fluid culture for pathogens. Therapeutic options included endoscopic trans-urethral incision or trans-perineal aspiration under ultrasound guidance, or conservative therapy. Of the 24 patients studied, 45.83% of the cases had a pre-disposing factor, and diabetes mellitus (37.50%) was the most common. Digital rectal palpation revealed fluctuation in 70.83% of the cases. Trans-abdominal ultrasonography missed the condition in 29.16% of the cases. On TRUS, all the study patients showed hypo-echoic zones, while nine others showed internal septations. In most of the cases, the lesion was peripheral. A causative pathogen could be identified in 70.83% of the cases. Surgical drainage of the abscess by trans-urethral deroofing was performed in 17 cases (including one with failed aspiration), trans-perineal aspiration under TRUS guidance was performed in three cases and conservative therapy was followed in five cases. Our data confirms the importance of predisposing factors in the pathogenesis of prostatic abscess. In most of the cases, the clue to diagnosis is obtained by digital rectal palpation. TRUS gives the definite diagnosis and also helps in follow-up of patients. Trans-urethral deroofing is the ideal therapy where the abscess cavity is more than 1 cm, although in some selected cases, TRUS-guided aspiration or conservative therapy does have a role in treatment.