[A case of disseminated tuberculosis presenting as a metastasizing tumor, complicated by toxic megacolon caused by Clostridium difficile: Difficulties in diagnosis]. / Metasztatizáló tumor képét adó disszeminált tuberkulózis Clostridium difficile okozta toxicus megacolonnal szövodött esete: a diagnózis nehézségei.

A mára ritkán eloforduló tuberkulózis (tbc) extrapulmonális manifesztációi elorehaladott rosszindulatú daganatok képét utánozhatják, jelentos diagnosztikus dilemmákat okozva. A tbc igazolása gyakorta bonyolult, komplex vizsgálatokat igényel. Egy fiatal vietnámi nobeteg esetét ismertetjük, aki idült hasi fájdalom, fogyás, fejfájás, bal oldali hemiparesis miatt jelentkezett kórházunkban. Az urgens vizsgálatok hasi folyadékgyülemek, lymphadenopathia és peritonealis carcinosis képe mellett az uterushoz asszociált ökölnyi kismedencei térfoglaló képletet, intracranialisan agyödémát és metastaticusnak tuno gócokat ábrázoltak. Neurológiai, belgyógyászati, majd pulmonológiai klinikai vizsgálatok és kezelések során eloször disszeminált gynaecologiai tumor, majd meningealis-, miliaris tüdo- és kiterjedt hasüregi-kismedencei érintettséggel járó tbc gyanúja fogalmazódott meg. Bár mycobactérium jelenléte nem volt igazolható, antituberculoticus- és komplex antibiotikus terápiát alkalmaztak. Ennek szövodményeként Clostridium difficile okozta enterocolitis alakult ki. Átmeneti állapotrosszabbodás miatti intenzív osztályos kezelést követoen a beteget visszahelyezték kórházunk belgyógyászatára. Itt toxicus megacolon, acut peritonitis alakult ki, emiatt sürgos mutétet végeztünk.A hasüregben granulomatosus peritonitis encapsulans, extrém tágult, megrepedt taeniájú colon, hyperaemiás vékonybéltraktus, tuboovarialis tályogok voltak láthatók. Oncotomiát követoen salpingo-oophorectomiát és subtotalis colectomiát végeztünk, Brooke szerinti ileostomát készítettünk. Az intenzív osztályos, majd infektológiai kezelésnek köszönhetoen a beteg reconvalescentiája sikeres volt, kielégíto állapotban emittálták. A specimenek valós ideju PCR-vizsgálata során Mycobacterium DNS nem volt detektálható, végül a hasüregi váladék és granulomák mikroszkópos vizsgálatával sikerült saválló pálcákat identifikálni.Az eset kapcsán áttekintjük az extrapulmonális tbc diagnosztikus lehetoségeit és terápiás nehézségeit.

The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1.

Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders breast cancer cells and insulin deficient mice to have higher IR/IGF1R ratio by positively and negatively regulating IR and IGF1R expression at the protein level, respectively. TRIP-Br1 repressed IR degradation by suppressing its ubiquitination. Meanwhile, TRIP-Br1 directly interacts with both IGF1R and NEDD4-1 E3 ubiquitin ligase, in which TRIP-Br1/NEDD4-1 degrades IGF1R via ubiquitin/proteasome system. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio.

SERTAD1 Sensitizes Breast Cancer Cells to Doxorubicin and Promotes Lysosomal Protein Biosynthesis.

Acquired chemoresistance of tumor cells is an unwanted consequence of cancer treatment. Overcoming chemoresistance is particularly important for efficiently improving cancer therapies. Here, using multiple lines of evidence, we report the suppressive role of SERTAD1 in apoptosis/anoikis. Among various breast cancer cell lines, higher SERTAD1 expression was found in MCF7 and MDA-MB-231 in suspension than in adherent cell culture. We revealed an unexpected phenomenon that different types of cell deaths were induced in response to different doses of doxorubicin (Dox) in breast cancer cells, presumably via lysosomal membrane permeabilization. A low dose of Dox highly activated autophagy, while a high dose of the chemotherapy induced apoptosis. Inhibition of SERTAD1 promoted the sensitivity of breast cancer cells to Dox and paclitaxel, leading to a significant reduction in tumor volumes of xenograft mice. Simultaneously targeting cancer cells with Dox and autophagy inhibition successfully induced higher apoptosis/anoikis. The novel role of SERTAD1 in maintaining cellular homeostasis has also been suggested in which lysosomal contents, including LAMP1, LAMP2, CTSB, and CTSD, were reduced in SERTAD1-deficient cells.

Multi-material digital light processing bioprinting of hydrogel-based microfluidic chips.

Recent advancements in digital-light-processing (DLP)-based bioprinting and hydrogel engineering have enabled novel developments in organs-on-chips. In this work, we designed and developed a multi-material, DLP-based bioprinter for rapid, one-step prototyping of hydrogel-based microfluidic chips. A composite hydrogel bioink based on poly-ethylene-glycol-diacrylate (PEGDA) and gelatin methacryloyl (GelMA) was optimized through varying the bioprinting parameters such as light exposure time, bioink composition, and layer thickness. We showed a wide range of mechanical properties of the microfluidic chips for various ratios of PEGDA:GelMA. Microfluidic features of hydrogel-based chips were then tested using dynamic flow experiments. Human-derived tumor cells were encapsulated in 3D bioprinted structures to demonstrate their bioactivity and cell-friendly environment. Cell seeding experiments then validated the efficacy of the selected bioinks for vascularized micro-tissues. Our biofabrication approach offers a useful tool for the rapid integration of micro-tissue models into organs-on-chips and high-throughput drug screening platforms.

Cassava breeding and agronomy in Asia: 50 years of history and future directions.

In Asia, cassava (Manihot esculenta) is cultivated by more than 8 million farmers, driving the rural economy of many countries. The International Center for Tropical Agriculture (CIAT), in partnership with national agricultural research institutes (NARIs), instigated breeding and agronomic research in Asia, 1983. The breeding program has successfully released high-yielding cultivars resulting in an average yield increase from 13.0 t ha-1 in 1996 to 21.3 t ha-1 in 2016, with significant economic benefits. Following the success in increasing yields, cassava breeding has turned its focus to higher-value traits, such as waxy cassava, to reach new market niches. More recently, building resistance to invasive pests and diseases has become a top priority due to the emergent threat of cassava mosaic disease (CMD). The agronomic research involves driving profitability with advanced technologies focusing on better agronomic management practices thereby maintaining sustainable production systems. Remote sensing technologies are being tested for trait discovery and large-scale field evaluation of cassava. In summary, cassava breeding in Asia is driven by a combination of food and market demand with technological innovations to increase the productivity. Further, exploration in the potential of data-driven agriculture is needed to empower researchers and producers for sustainable advancement.

2'-Hydroxycinnamaldehyde induces apoptosis through HSF1-mediated BAG3 expression.

BAG3, a member of BAG co-chaperone family, is induced by stressful stimuli such as heat shock and heavy metals. Through interaction with various binding partners, BAG3 is thought to play a role in cellular adaptive responses against stressful conditions in normal and neoplastic cells. 2'-Hydroxycinnamaldehyde (HCA) is a natural derivative of cinnamaldehyde and has antitumor activity in various cancer cells. In the present study, for the first time, we identified that HCA induced BAG3 expression and BAG3-mediated apoptosis in cancer cells. The apoptotic cell death induced by HCA was demonstrated by caspase-7, -9 and PARP activation, and confirmed by Annexin V staining in both SW480 and SW620 colon cancer cells. Notably, both the mRNA and protein levels of BAG3 were largely induced by HCA in a dose- and time-dependent manner. By showing transcription factor HSF1 activation, we demonstrated that HCA induces the expression of BAG3 through HSF1 activation. More importantly, knockdown of BAG3 expression using siRNA largely inhibited HCA-induced apoptosis, suggesting that BAG3 is actively involved in HCA-induced cancer cell death. Considering the importance of the stress response mechanism in cancer progression, our results strongly suggest that BAG3 could be a potential target for anticancer therapy.