Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.

Sine oculis homeoprotein 1 (SIX1), a prominent representative of the homeodomain transcription factors within the SIX family, has attracted significant interest owing to its role in tumorigenesis, cancer progression, and prognostic assessments. Initially recognized for its pivotal role in embryonic development, SIX1 has emerged as a resurgent factor across a diverse set of mammalian cancers. Over the past two decades, numerous investigations have emphasized SIX1's dual significance as a developmental regulator and central player in oncogenic processes.

Accelerating Formulation Design via Machine Learning: Generating a High-throughput Shampoo Formulations Dataset.

Liquid formulations are ubiquitous yet have lengthy product development cycles owing to the complex physical interactions between ingredients making it difficult to tune formulations to customer-defined property targets. Interpolative ML models can accelerate liquid formulations design but are typically trained on limited sets of ingredients and without any structural information, which limits their out-of-training predictive capacity. To address this challenge, we selected eighteen formulation ingredients covering a diverse chemical space to prepare an open experimental dataset for training ML models for rinse-off formulations development.

Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice.

The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs.

A peek into the population genetics of white teatfish (Holothuria fuscogilva) of Kenya's south coast.

Background: The white teatfish, Holothuria fuscogilva, is widely distributed in coastal areas, including waters around coral reefs and seagrasses in the Indo-Pacific. In Kenya, the species is distributed in shallow reefs with higher landings reported from the Vanga-Shimoni-Gazi seascape on the Kenyan south coast. Despite its high exploitation for export and its vulnerable and endangered statuses under IUCN and CITES respectively, Kenya's H.

A dynamic knowledge graph approach to distributed self-driving laboratories.

The ability to integrate resources and share knowledge across organisations empowers scientists to expedite the scientific discovery process. This is especially crucial in addressing emerging global challenges that require global solutions. In this work, we develop an architecture for distributed self-driving laboratories within The World Avatar project, which seeks to create an all-encompassing digital twin based on a dynamic knowledge graph.

Racial differences in serum chemokines in prostate cancer patients.

Background: This study aimed to understand the differential levels of inflammatory chemokines in association with higher prostate cancer incidence and mortality in African American (AA) men than in Caucasians (CA).

Methods: The authors used a chemokine assay to simultaneously measure 40 chemokines and cytokines levels in the serum of preoperative prostate cancer patients and healthy controls of AA and CA races. Selected chemokines (CXCL2, CXCL5, and CCL23) serum level was validated in 211 serum samples from prostate cancer patients and healthy controls.

DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway.

Epigenetic alterations such as DNA methylation and histone modifications are implicated in repressing several tumor suppressor genes in prostate cancer progression. In this study, we determined the anti-prostate cancer effect of a small molecule drug guadecitabine (gDEC) that inhibits/depletes the DNA methylation writer DNA methyltransferase 1 (DNMT1). gDEC inhibited prostate cancer cell growth and proliferation in vitro without activating the apoptotic cascade.

Effect of Different Doses of Buprenorphine in Combination with Bupivacaine in the Management of Postoperative Analgesia: A Comparative Study.

Background: Longer duration of analgesia, ceiling effect on respiratory depression, and the antihyperalgesia property make buprenorphine a good adjuvant for managing moderate-to-severe postoperative pain.

Aims: The aim of this study is to evaluate the onset and duration of postoperative analgesia of three different doses of buprenorphine of 60, 100, and 150 μg given intrathecally along with hyperbaric bupivacaine in patients undergoing lower limb surgeries.

Setting And Design: This prospective observational study was carried out in the anesthesia department of a tertiary care hospital.

Pronounced Suppression and X-Pattern Merging of Equatorial Ionization Anomalies After the 2022 Tonga Volcano Eruption.

Following the 2022 Tonga Volcano eruption, dramatic suppression and deformation of the equatorial ionization anomaly (EIA) crests occurred in the American sector ∼14,000 km away from the epicenter. The EIA crests variations and associated ionosphere-thermosphere disturbances were investigated using Global Navigation Satellite System total electron content data, Global-scale Observations of the Limb and Disk ultraviolet images, Ionospheric Connection Explorer wind data, and ionosonde observations. The main results are as follows: (a) Following the eastward passage of expected eruption-induced atmospheric disturbances, daytime EIA crests, especially the southern one, showed severe suppression of more than 10 TEC Unit and collapsed equatorward over 10° latitudes, forming a single band of enhanced density near the geomagnetic equator around 14-17 UT, (b) Evening EIA crests experienced a drastic deformation around 22 UT, forming a unique X-pattern in a limited longitudinal area between 20 and 40°W.

CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma.

Endoplasmic reticulum (ER) stress is a cellular process in response to stress stimuli in protecting functional activities. However, sustained hyperactive ER stress influences tumor growth and development. Hepatocytes are enriched with ER and highly susceptible to ER perturbations and stress, which contribute to immunosuppression and the development of aggressive and drug-resistant hepatocellular carcinoma (HCC).

RSK1 vs. RSK2 Inhibitory Activity of the Marine β-Carboline Alkaloid Manzamine A: A Biochemical, Cervical Cancer Protein Expression, and Computational Study.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia, and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, SIX1, and vacuolar ATPases. We hypothesized that additional, yet undiscovered molecular targets might be associated with Manzamine A's (MZA) reported pharmacological properties. We report here, for the first time, that MZA selectively inhibited a 90 kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases, while in vitro RSK kinase assays demonstrated a 10-fold selectivity in the potency of MZA against RSK1 versus RSK2.

A Perspective on Modulating Antitumor Immunity in Targeting Prostate Cancer.

Medicinal plants serve as a lead source of bioactive compounds and have been an integral part of day-to-day life in treating various disease conditions since ancient times. Withaferin A (WFA), a bioactive ingredient of , has been used for health and medicinal purposes for its adaptogenic, anti-inflammatory, and anticancer properties long before the published literature came into existence. Nearly 25% of pharmaceutical drugs are derived from medicinal plants, classified as dietary supplements.

Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity.

In this study, we investigated the potential of MIC-1 (macrophage inhibitory cytokine-1) on the severity of prostate cancer between African American men and Caucasians. Differences between the races were examined using Mann-Whitney tests for continuous variables and Fisher's exact tests for categorical variables. Pearson's correlation coefficient was used to identify associations between continuous measures across all samples and within each race.

2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned.

The Marine Natural Product Manzamine A Inhibits Cervical Cancer by Targeting the SIX1 Protein.

Natural products remain an important source of drug leads covering unique chemical space and providing significant therapeutic value for the control of cancer and infectious diseases resistant to current drugs. Here, we determined the antiproliferative activity of a natural product manzamine A () from an Indo-Pacific sponge following various in vitro cellular assays targeting cervical cancer (C33A, HeLa, SiHa, and CaSki). Our data demonstrated the antiproliferative effects of at relatively low and non-cytotoxic concentrations (up to 4 μM).

Effect of Dexmedetomidine as an Adjuvant to Ropivacaine in Ilioinguinal-Iliohypogastric Nerve Blocks for Inguinal Hernia Repair in Pediatric Patients: A Randomized, Double-Blind, Control Trial.

Background: Bulk of published data support the efficacy of dexmedetomidine for prolongation of peripheral nerve block; but most of the studies are in adults. Ample data regarding use of dexmedetomidine in setting of paediatric peripheral nerve blocks is scarce.

Aim And Objective: To determine whether adding dexmedetomidine to ropivacaine in ilioinguinal-iliohypogastric nerve block prolongs postoperative analgesia in children undergoing inguinal hernia repair.

Inflammasomes: Emerging Central Players in Cancer Immunology and Immunotherapy.

Inflammation has an established role in cancer development and progression and is a key player in regulating the entry and exit of immune cells in the tumor microenvironment, mounting a significant impact on anti-tumor immunity. Recent studies have shed light on the role of inflammasomes in the regulation of inflammation with a focus on the subsequent effects on the immunobiology of tumors. To generate strong anti-tumor immunity, cross-talk between innate, and adaptive immune cells is necessary.

Comparison of Palonosetron, Dexamethasone, and Palonosetron Plus Dexamethasone as Prophylactic Antiemetic and Antipruritic Drug in Patients Receiving Intrathecal Morphine for Lower Segment Cesarean Section.

Background: Intrathecal morphine is commonly used for postcesarean analgesia. Its use is frequently associated with opioid-induced nausea, vomiting, and pruritus. Palonosetron (0.

Withaferin A Associated Differential Regulation of Inflammatory Cytokines.

A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA). Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines.

Guidelines for medical management of nuclear/radiation emergencies.

Management of victim of radiation injury poses a wide spectrum of challenges to the health care provider starting with the evaluation of the damage, the kind of hospitalization and treatment and the regular monitoring of the patient. Undesirable clinical outcomes are probable if prodromal stage evolves rapidly and is severe. Critical systems like neurovascular, gastrointestinal, haematopoietic and cutaneous are afflicted in Acute Radiation Syndrome.

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad-PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic.

Expression analysis of inflammasome sensors and implication of NLRP12 inflammasome in prostate cancer.

Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines.

From Inflammation to Prostate Cancer: The Role of Inflammasomes.

Inflammation-associated studies entice specific attention due to inflammation's role in multiple stages of prostate cancer development. However, mechanistic regulation of inflammation inciting prostate cancer remains largely uncharacterized. A focused class of inflammatory regulators known as inflammasomes has recently gained attention in cancer development.