Human organic anion transporting polypeptide (OATP) 1B1 and 1B3 are two highly homologous liver-specific uptake transporters. However, 2’,7’-dichlorofluorescein (DCF) is preferably transported by OATP1B1. In the present study, the molecular mechanisms for the selective transport of DCF by OATP1B1 were investigated by constructing and characterizing an array of OATP1B1/1B3 chimeras and site-directed mutagenesis. Our results show that transmembrane domain (TM) 10 is crucial for the surface expression and function of OATP1B1, in which Q541 and L545 play the most important roles in DCF transport. Replacement of TM10 in OATP1B1 with its OATP1B3 counterpart led to OATP1B1’s complete intracellular retention. Q541 and L545 may interact with DCF directly via hydrogen bonding and hydrophobic interactions. The decrease of DCF uptake by Q541A and L545S was due to their reduced binding affinity for DCF as compared with OATP1B1. In addition, Q541 and L545 are also crucial for the transport of estradiol-17β-glucuronide (E17βG) but not for the transport of estrone-3-sulfate (E3S), indicating different interaction modes between DCF/E17βG and E3S in OATP1B1. Taken together, Q541 and L545 in TM10 are critical for OATP1B1-mediated DCF uptake, but their effect is substrate-dependent.

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2–57 days old) and human hepatocytes (pediatric liver tissue donors: age 2–12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate. mRNA expression was determined in rat liver tissue corresponding to rat ages used in the functional studies, while hOCT1 mRNA expressions were determined in the same hepatocyte batches as those used for uptake studies. Maturation of rOct/hOCT activity and expression were evaluated by comparing values obtained at the various ages to the adult values. Relative to adult values (at 8 weeks), ASP⁺ uptake clearance in suspended rat hepatocytes aged 0, 1, 2, 3, 4, 5, and 6 weeks reached 26%, 29%, 33%, 37%, 72%, 63%, and 71%, respectively. Hepatic Oct1 mRNA expression was consistent with Oct activity (correlation coefficient of 0.92). In human hepatocytes, OCT1 activity was age dependent and also correlated with mRNA levels (correlation coefficient of 0.88). These data show that Oct1/OCT1 activities and expression mature gradually in rat/human liver, thereby mirroring the expression pattern of organic anion transporting polypeptide in rat. These high-resolution transporter ontogeny profiles will allow for more accurate prediction of the pharmacokinetics of OCT1/Oct1 substrates in pediatric populations and juvenile animals.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

THE Federal Bureau of Investigation is probing a possible computer hacking attack on J.P. Morgan Chase & Co.

Disaster was averted at a Kentucky hospital when an ostensibly deceased organ donor began “thrashing” around in the operating theater, a preservationist tells NPR.

“He was moving around,” Natasha Miller recalled of the patient, whom NPR identified as Anthony Thomas “TJ” Hoover II. “He was crying visibly.”

The two surgeons assigned to the transplant naturally refused to go through with the procedure, which was reportedly scheduled to take place at Baptist Health Richmond Hospital in October 2021. But when her colleague called Kentucky Organ Donor Affiliates, which coordinated the harvest, Miller said the supervisor told them they “were going to do the case” and needed to “find another doctor.”

Read more at The Daily Beast.

One day, doctors might be able to 3D print copies of your organs in order to test a variety of drugs, thanks to a new technique that uses light and sound for rapid printing

Kurt "CyberGuy" Knutsson shares tips and suggestions for how to get the best use out of the updated Calendar app available with the latest iOS update.

Rubbing a common yellow food dye onto a mouse's skin turns it temporarily transparent, so we can monitor its insides without harming the animal

After tackling the best party games on Switch in 2024, the recent release of Emio – The Smiling Man: Famicom …

Continue reading "The Best Switch Visual Novels and Adventure Games in 2024 – From Fata Morgana and VA-11 Hall-A to Famicom Detective Club and Gnosia"

L’ex-premier ministre de la Colombie-Britannique John Horgan est décédé à l’âge de 65 ans après une bataille contre le cancer.

Former B.C. premier John Horgan has died at the age of 65, CBC News has confirmed. In June this year, Horgan told CBC that he had been diagnosed with cancer for the third time during a routine followup appointment for his previous throat cancer.

The office of the Additional Director General of Foreign Trade (CLA DGFT) has announced an Export Obligation Discharge Certificate (EODC) Camp scheduled from November 11 to 22, 2024. The camp is

As part of the National Pharmacy Week (NPW) celebration, the Kerala Private Pharmacist Association (KPPA) is organizing a high─impact webinar series from November 17th to 23rd, connected by the common

Access to care isn’t enough. Healthcare organizations need to build trust in order to reach underserved communities, experts said on a recent panel.

The post How Can Healthcare Organizations Earn Trust with Marginalized Communities? appeared first on MedCity News.

Yesterday’s conference sessions surfaced interesting questions and approaches regarding the post-acute sector, bundled payment, emergency medicine and anesthesia. Post-Acute Focus: With more and more focus on the need to rationalize and re-organize the post-acute sector, we have seen multiple industry leaders start to evolve their strategies.  I blogged yesterday about AccentCare’s interesting strategy in the...… Continue Reading

A large amount of wind, much discussion about the U.S healthcare, and the public getting soaked again – if you were thinking about Washington, DC and the new Congress, you’re 3,000 miles away from the action. This is the week of the annual JP Morgan Healthcare conference in San Francisco, with many thousands of healthcare...… Continue Reading

Addressing the Social Determinants of Health:  Is the healthcare industry pushing a rock up a hill?  We collectively are trying to provide healthcare with improved quality and reduced cost, but the structure of the nation’s healthcare system remains heavily siloed with the social determinants of health often falling wholly or partly outside the mandate and...… Continue Reading

Day 3 of the JPMorgan healthcare conference was one of striking contrasts between the old and the new. (And, by the way, the rain finally stopped for a day, but it will be back tomorrow to finish off the last day of the conference). The Old:  Sitting in the Community Health Systems (CHS) presentation and...… Continue Reading

Some interesting presentations on the last day of the JPMorgan Healthcare Conference that concentrated on common themes – the increasing importance of ancillary business line to bolster core business revenue and of filling in holes to achieve scale and full-service offerings. Genesis Healthcare – The largest U.S. skilled nursing facility (SNF) provider, which also is...… Continue Reading

Apr 9, 2024

On April 2, the study group met for the second time to evaluate the role of international humanitarian groups in shaping political and social outcomes in Africa. The group examined how these organizations deal with emergencies, crises, and conflict situations across the continent, and scrutinized their influence on policy decisions and discuss the potential benefits and drawbacks of their involvement. Discussions covered the expanding influence of organizations like the United Nations High Commissioner for Refugees (UNHCR), Médecins Sans Frontières (Doctors Without Borders), and the International Rescue Committee (ICR). The study group counted with the presence of external expert guest Professor Sabs K. Quereshi, a senior-level leader with 17+ years of experience in global health, gender equality, health policy and equity, national security, humanitarian response, and government and multilateral affairs sectors in the U.S., with the UN, and worldwide.

Here are a few organizations that need our support right now: 

Fund Texas Choice. A nonprofit organization funding abortion travel for people in Texas. 

Frontera Fund. Making abortion accessible for people in the Rio Grande Valley. 

Clinic Access Support Network. Providing transportation, lodging, emotional support, and more to those seeking abortion care in Houston, TX. 

Bridge Collective. A full spectrum doula collective, nonprofit organization based in Austin, TX. 

The Afiya Center. An advocacy organization based in Dallas, TX, dedicated to transforming the lives of Black womxn and girls through reproductive justice. 

Texas Equal Access Fund. Providing financial and emotional support to people seeking abortion care in the north, east, and panhandle regions of Texas. 

Lilith Fund. Financial assistance, emotional support, and building community spaces for people who need abortions in Texas — unapologetically, with compassion and conviction. 

West Fund. Working to make abortions accessible and affordable to people in West Texas. 

Thank you to the folks at @FundTexasChoice who helped me compile this list.

DNA analysis suggests Pando, a quaking aspen in Utah with thousands of stems connected by their roots, is between 16,000 and 81,000 years old

One day, doctors might be able to 3D print copies of your organs in order to test a variety of drugs, thanks to a new technique that uses light and sound for rapid printing

The International Monetary Fund has collated information on the tax and non-tax policy responses of some 193 jurisdictions to COVID-19.

Highlights: Significant budget growth reflects societal recognition and commitment to organ transplantation Enhanced

A recent judgement by allows an organ failure patient from outside Gujarat to register on the state registry. On Monday, the Gujarat high court issued

bHighlights:/bul class="group-list punch-points"liThe Transplantation of Organs Act, 1994 and its subsequent Rules and Amendments is the supreme

Colombo.25 July 2013. At the request of the Central Environmental Authority (CEA), the International Water Management Institute (IWMI) signed an agreement to collaborate towards Resource Recovery and Reuse in Sri Lanka. IWMI and CEA join hands in targeting two main challenges that Sri Lanka is currently facing: Urban waste management; and the need to increase […]

The post CEA partners with IWMI to turn organic waste into high-quality fertilizer first appeared on International Water Management Institute (IWMI).

Colombo, December 10, 2013. At the request of the Colombo Municipal Council (CMC), the Central Environmental Authority (CEA), in collaboration with the International Water Management Institute (IWMI), organized a stakeholder meeting to discuss improvements that can be made to the management of municipal waste in the City of Colombo. The meeting was held at the […]

The post CEA partners with IWMI to improve Colombo’s municipal waste management and farmers’ access to organic fertilizers first appeared on International Water Management Institute (IWMI).

Amidst soaring pollution levels in Delhi, health experts warned on Saturday that poor air quality can adversely impact all our organs. A layer of smog

Tiny, self-organized three-dimensional (3D) tissue cultures (Organoids) derived from medlinkstem cells/medlink have been developed to produce teeth-protecting

bHighlights:/bul class="group-list punch-points"li MOHAN Foundation was awarded the title of the best NGO for its outstanding contributions to

Union Health Minister Mansukh Mandaviya announced that the Indian government has implemented several initiatives to boost medlinkorgan donations/medlink in the country.

All India Institute of Medical Sciences (AIIMS) Director, M. Srinivas, advocates dispelling myths about medlinkorgan donation/medlink and emphasizes

Doctors urge India to raise medlinkorgan donation/medlink awareness due to critical supply shortage ahead of World Organ Donation Day with a dismal donation rate of 0.

bHighlights:/bul class="group-list punch-points"li MOHAN Foundation's "Drive to Save Lives" golf tournament was held on September 9, 2023/li liIt

The Ministry of Health and Family Welfare announced that approximately 10,000 individuals are anticipated to commit to medlinkorgan donation/medlink on September 16 (!--ref1--).

Research suggests that neonatal kidney transplantation could be a game-changing solution to the organ shortage crisis, highlighting the emotional challenges faced by families.

bHighlights:/bul class="group-list punch-points"li Indian Chief Minister M.K. Stalin announces full state honors for organ donors, recognizing

medlinkZebrafish/medlink exhibits a crucial role in the fields of solid organ preservation and transplantation, especially with respect to experimental transplantation efforts.

bHighlights:/bul class="group-list punch-points"li GMCH in Guwahati pioneers deceased kidney transplants in Northeast India/li liErnakulam

The Karnataka government is in the process of formulating a policy similar to Tamil Nadu State's organ donation policy to honor organ donors and their

bHighlights:/bul class="group-list punch-points"li 93% of organ donations come from living donors, revealing a striking imbalance/li liWomen,

bHighlights:/bul class="group-list punch-points"li A 28-year-old man who was brain dead had his kidneys, lungs, and liver successfully transplanted

Health Minister Ma Subramanian disclosed on Saturday that 6,939 residents in Tamil Nadu are in line for medlinkorgan transplants/medlink (!--ref1--).

bHighlights:/bul class="group-list punch-points" liChildren and parents unite for organ donation awareness/li liInspiring stories of transplant

bHighlights:/bul class="group-list punch-points" liKids Dash, organized by Mohan Foundation to promote organ donation awareness/li liOver

Enhancements in organ preservation may alleviate the scarcity of hearts for transplantation, as over 5,000 hearts are transplanted annually worldwide,