Background
The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of ...drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish.
Methods
In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments.
Results
We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth.
Conclusions
Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.
β-caryophyllene (BCP), an essential oil component of many herbs and spices, has various biological activities as a functional food factor. A distinct feature of BCP is its volatile double-ring ...sesquiterpene structure. Orally administered BCP is reportedly detected in its intact form in mice serum; however, the distribution of inhaled volatile BCP throughout the body remains unknown. This study aimed to estimate the distribution properties of inhaled volatile BCP and to investigate its effects on metabolism. After mice were exposed to volatile BCP, it was detected in the lung, olfactory bulb, brain, serum, heart, liver, kidney, epididymal fat, and brown adipose tissue. BCP was further detected in the brain, liver, and brown adipose tissue 24 h after exposure. Metabolites related to glutathione metabolism were significantly altered in the liver. These results suggest that inhaled volatile BCP is widely distributed in murine tissues and affects the dynamics of metabolites in the liver.
A catalytic process for the chemo- and regioselective functionalization of nonprotected carbohydrates has been developed. This novel process allows selective thiocarbonylation, acylation, and ...sulfonylation of a particular hydroxy group in a particular carbohydrate in the simultaneous presence of structurally similar carbohydrates such as anomers. In addition, the chemoselectivity can be switched by regulating only the length of the alkyl chain in the organotin catalyst.
One, two, three, four: A copper(I)–phosphine complex catalyzes the diborylation of alkynes and arynes, and the tri‐ or tetraborylation of propargyl ethers (see scheme; pin=pinacolato). In the latter ...cases, the CO bond(s) as well as the CC bond are borylated in one pot. Furthermore, a diborylation product serves as an intermediate in the efficient synthesis of ortho‐terphenyls with pharmacological activity.
Regio‐ and stereoselective installation of boryl and stannyl moieties into a carbon–carbon triple bond of various alkynes has been achieved based on a three‐component coupling reaction by using a ...diboron and a tin alkoxide with the aid of a copper(II) acetate–tricyclohexylphosphine complex, giving diverse vic‐borylstannylalkenes in a straightforward manner. Carbon–tin and carbon–boron bonds of the resulting borylstannylation product are successively transformed into carbon–carbon bonds by a Migita–Kosugi–Stille and a Suzuki–Miyaura coupling, leading to the formation of (Z)‐tamoxifen with anti‐breast cancer activity.
Borylstannylation: A copper–tricyclohexylphosphine complex was found to catalyse the three‐component borylstannylation of alkynes with a diboron and a tin alkoxide to afford vic‐borylstannylalkenes in a regio‐ and stereoselective manner. Synthetic utility of the resulting borylstannylation product was demonstrated by a three‐step synthesis of (Z)‐tamoxifen from commercially available substrates by successive Migita–Kosugi–Stille and Suzuki–Miyaura couplings (see scheme).
Glycerol is the main side product in the biodiesel manufacturing process, and the development of glycerol valorization methods would indirectly contribute the sustainable biodiesel production and ...decarbonization. Transformation of glycerol to optically active C3 units would be one of the attractive routes for glycerol valorization. We herein present the asymmetric sulfonylative desymmetrization of glycerol by using a CuCN/(
,
)-PhBOX catalyst system to provide an optically active monosulfonylated glycerol in high efficiency. A high degree of enantioselectivity was achieved with a commercially available chiral ligand and an inexpensive carbonate base. The optically active monosulfonylated glycerol was successfully transformed into a C3 unit attached with differentially protected three hydroxy moieties. In addition, the synthetic utility of the present reaction was also demonstrated by the transformation of the monosulfonylated glycerol into an optically active synthetic ceramide, sphingolipid E.
Abstract
Turmerones (α-turmerone, β-turmerone, and ar-turmerone) are the major volatile compounds in turmeric (
Curcuma longa
), a perennial herb of the ginger family. We previously reported that ...inhaled volatile turmerones could be transferred in the blood and organs. However, the difference between the two pathways, oral administration and inhalation, and the effect of inhaled turmerones on biological activities remain unknown. In this study, we compared the distribution patterns of turmerones after oral administration and inhalation. The relative levels (concentrations of turmerones in each organ/serum) in the lung, olfactory bulb, brain, heart, kidney, and epididymal fat in the inhalation group tended to be, or are significantly, higher than in the oral administration group. The relative levels of brown adipose tissue in the inhalation group were lower than in the oral administration group. Long-term (50 days) inhalation to volatile turmerones suppressed weight gain and hypertrophy of adipocytes in the epididymal fat of mice fed a high-fat diet. These results suggest that inhaled turmerones can be incorporated into the organs of mice via different pathway from as to those from oral administration and can affect the biological function of the organs under certain conditions.
Vaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired ...humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination.
In total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression.
Significant associations were observed between seven SNPs in
, and
, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in
, and
were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in
, and
for the maintenance of antibody titers and that in
for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%).
The candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules.
Formal hydroboration of internal alkynes proceeds regio‐ and stereoselectively by the use of a diboron reagent masked with 1,8‐diaminonaphthalene (dan) in the presence of readily available ...(Ph3P)3CuCl, leading to direct formation of diverse B‐protected alkenylborons in high yield. The B(dan) moiety can also be efficiently installed into the CC double bond of alkenes to afford the respective alkylborons.
dan‐ned if you do: A convenient and potent method for forming CB(dan) bonds that depends on copper‐catalyzed formal hydroboration of alkynes and alkenes with a masked diboron reagent is described. dan=1,8‐diaminonaphthalene.
Nonprotected carbohydrates: The catalytic regioselective thiocarbonylation of carbohydrates by using organotin dichloride under mild conditions was demonstrated. The reaction afforded various deoxy ...saccharides in high yields and excellent regioselectivity in a minimum number of steps. The regioselectivity of the thiocarbonylation is attributed to the intrinsic character of the carbohydrates based on the stereorelationship of their hydroxy groups (see scheme).
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