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Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC via ROS-mediated damage in vitro. In vivo experiments further shows that silencing G6PD with lentivirus or non-viral gene delivery vector enhances oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus, this study indicates that G6PD is a potential prognostic biomarker and a promising target for CRC therapy.

A 12-year-old castrated male domestic shorthair cat was referred for respiratory distress. Physical examination revealed a systolic heart murmur at the left apex and crackles in all lung fields. Thoracic radiography showed Valentine-shaped cardiomegaly, pulmonary oedema, and pleural effusion. Echocardiography revealed focal thickening of the interventricular septum [11.01 mm; reference interval (RI) = 3.00-5.20 mm] and left ventricular posterior wall (7.41 mm; RI = 3.00-5.10 mm) during diastole. In the apex region, the free wall was focally thinned to approximately 1.6 mm with hypokinetic myocardial movement, indicating thin and hypokinetic myocardial segments. Additionally, decreased left atrial fractional shortening (12.5%; RI = 23.9-34.9%) and an increased left atrial-to-aortic ratio (2.87; RI = 0.88-1.43) were observed, along with spontaneous echocardiographic contrast in the left atrium, indicating increased thrombotic risk. The electrocardiogram showed a left axis deviation with small R waves and deep S waves in lead II, which is consistent with a left anterior fascicular block caused by delayed conduction in the left anterior fascicle. This case report describes the coexistence of a left anterior fascicular block and thin, hypokinetic myocardial segments in feline hypertrophic cardiomyopathy, suggesting a possible pathophysiological link.

Background: To compare the imaging and clinical features of temporal lobe necrosis (TLN) in nasopharyngeal carcinoma (NPC) patients treated with two-dimensional radiotherapy (2D-RT) or those with intensity-modulated radiotherapy (IMRT). Methods: We retrospectively analysed NPC patients who underwent 2D-RT (72 patients, 128 temporal lobes) or IMRT (36 patients, 50 lobes) and developed radiation-induced, MRI-confirmed TLN. Results: White-matter lesions (WMLs), contrast-enhanced lesions, cysts and local mass effects were present in 128 out of 128 vs 48 out of 50 ( P =0.078), 123 out of 128 vs 47 out of 50 ( P =0.688), 10 out of 128 vs 1 out of 50 ( P =0.185) and 57 out of 128 vs 13 out of 50 ( P =0.023) temporal lobes, respectively, in the 2D-RT and IMRT groups. The WMLs were more extensive in the 2D-RT group ( P <0.001). The maximum diameter of contrast-enhanced lesions was greater in the 2D-RT group ( P <0.001), and these lesions tended to extend far away from the nasopharynx. The WMLs and enhancement had no impact on cyst development (both P =1). Local mass effects were always accompanied with contrast-enhanced lesions ( P =0.024) but were not correlated with WMLs or cysts ( P =0.523 and 0.341, respectively). There were no between-group differences in clinical features (all P -values>0.05), whereas the difference in the incidence of severe debility was of marginal significance (18.1% vs 5.6%, P =0.077). Conclusions: The IMRT-induced TLN was less extensive and milder than 2D-RT-induced TLN, but both had similar clinical features.

Early in the exploration of the chemical nature of life, it was widely believed that the molecules of living organisms, by their very nature, differ from those of inorganic material molecules and possess a vital force (‘ élan vital’ ). Similarly, early scientific thinking on the subject of cell death and its induction by cytotoxic cells of the immune system was pervaded by a sense that the molecules mediating these functions possess intrinsic deadly activity and are dedicated exclusively to death-related tasks. This impression was also reflected in the initial notions of the mode of action of intracellular proteins that signal for death. It is now gradually becoming clear, however, that proteins participating in death induction also have functions unrelated to death. Nevertheless, as exemplified by studies of the function of caspase-8 (an enzyme that signals both for activation of the extrinsic cell-death pathway and for non-death-related effects), analysis of the mechanistic basis for such heterogeneity might allow identification of distinct structural determinants in the proteins participating in death induction that do bear death specificity.

This study was performed to induce atopic dermatitis (AD) using nongenetically predisposed Beagle dogs. Five healthy Beagle dogs were used. Twice weekly for 12 weeks, the dogs were painted on the axillae and groin with a solution of  ( ). Each dog was thereafter placed in a cage where a house dust mite (HDM) solution was applied on the bottom of the cage. The dog remained in the cage for 3 h daily for 3 consecutive days for the environmental exposure to HDM. Serum samples were collected at 0 week and 6 weeks after sensitisation, and at 0 h and 72 h after the environmental exposure. During the environmental exposure, skin biopsies were obtained at 0 h, 36 h, and 72 hours. After the first environmental exposure, no dog had any marked clinical sign. An additional sensitisation was subsequently administered for 10-13 weeks. Three of the five dogs developed pruritic dermatitis with skin lesions after the second exposure. The histopathology of the lesions revealed severe infiltration of inflammatory cells and dermal oedema. The levels of  -specific IgE were also elevated. This study demonstrated that AD could be induced by epicutaneous sensitisation with HDM in nongenetically predisposed dogs.

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.

Our previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro , and inhibited xenograft tumor growth and lung metastasis in vivo . MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment.

In the development of short fallow systems as alternatives to shifting cultivation in West Africa, a long-term trial was established at the International Institute of Tropical Agriculture (IITA) on an Alfisol in the forest-savanna transitional zone of southwestern Nigeria, comparing three fallow systems; natural regrowth fallow, cover crop fallow and alley cropping on soil productivity and crop yield sustainability. The natural fallow system consisted of natural regrowth of mainly Chromolaena odorata shrub as fallow vegetation. The cover crop fallow system consisted of Pueraria phaseoloides, a herbaceous legume as fallow vegetation. The alley cropping system consisted of woody hedgerows of Leucaena leucocephala as fallow vegetation. The fallow lengths were 0 (continuous cropping), 1, 2 and 3 years after 1 year of maize/cassava intercropping. Biomass produced from natural fallow and cover crop fallow was burnt during the land preparation. Fertilizer was not applied throughout the study. Without fertilizer application, maize yield declined from above 3.0 t ha−1 to below 0.5 t ha−1 during 12 years of cultivation (1989–2000) on a land cleared from a 23-year old secondary forest. Temporal change in cassava tuber yield was erratic. Mean maize grain yields from 1993–2000 except for 1999 were higher in cover crop fallow system (1.89 t ha−1) than in natural fallow system (1.73 t ha−1), while natural fallow system outperformed alley cropping system (1.46 t ha−1). During the above 7 years, mean cassava tuber yield in cover crop system (7.7 t ha−1) did not differ from natural fallow system (8.2 t ha−1), and both systems showed higher cassava tuber than the alley cropping system (5.7 t ha−1). The positive effect of fallowing on crop yields was observed for both crops in the three systems, however, insignificant effects were seen when fallow length exceeded 1 year for cover crop and alley cropping, and 2 years for natural fallow. Soil pH, organic carbon, available P and exchangeable Ca, Mg and K decreased considerably after 12 years of cultivation, even in a 3-year fallow subplot. After 12 years, soil organic carbon (SOC) within 0–5 cm depth in alley cropping (13.9 g kg−1) and natural fallow (13.7 g kg−1) was higher than in cover crop fallow (11.6 g kg−1). Whereas significant increase in SOC with either natural fallow or alley cropping was observed only after 2 or 3 years of fallow, the SOC in the 1-year fallow alley cropping subplot was higher than that in continuous cropping natural fallow subplot. It can be concluded from our study that in transforming shifting cultivation to a permanent cropping, fallow with natural vegetation (natural fallow), herbaceous legumes (cover crop fallow) and woody legumes (alley cropping) can contribute to the maintenance of crop production and soil fertility, however, length of fallow period does not need to exceed 2 years. When the fallow length is reduced to 1 year, a better alternative to natural regrowth fallow would be the cover crop for higher maize yield and alley cropping for higher soil organic matter. For fallow length of 2 years, West African farmers would be better off with the natural fallow system.

Legume cover crops are a potential means for overcoming N depletion in the derived savanna of West Africa. A 3-year trial was, therefore, conducted near Ibadan, southwestern Nigeria to measure the N contribution of 13 legume cover crops as compared to urea -N, using a N fertilizer replacement index for a maize test crop. Two series of trials involved the following legume cover crop species: Aeschynomene histrix, Centrosema brasilianum, Centrosema pascuorum, Chamaecrista rotundifolia, Cajanus cajan, Crotalaria verrucosa, Crotalaria ochroleuca, Lablab purpureus, Mucuna pruriens, Psophocarpus palustris, Pseudovigna argentea, Puer aria phaseoloides and Stylosanthes hamata. Trials were undertaken using a complete block design. Cover crops were planted in 1994 (Series 1) and 1995 (Series 2) in separate sites and each series was subsequently slashed and planted for one season with maize (Zea mays) in 1995 and 1996. At the 50% flowering stage, N concentration of above-ground vegetation of cover crops ranged from 21 to 38 g N kg⁻¹. Nitrogen accumulated by 4.5-month old cover crops ranged from 14 to 240 kg N ha⁻¹, depending on species and year. Cover crops increased grain yield of the subsequent maize crop by 25-136% over the control without N application. Nitrogen uptake by the maize crop was higher following cover crops than after maize or natural grass. The N fertilizer replacement index of cover crops for maize ranged from 11 (A. histrix) to 96 kg N ha⁻¹ (C. cajan) in Series 2. Perennial (C. brasilianum, S. hamata, C. cajan, P. phaseoloides and C. verrucosa) and annual (C. rotundifolia, M. pruriens, C. ochroleuca and L. purpureus) species could potentially save 50 to 100 kg N ha⁻¹ for maize crops. The cover crops accumulated more N in the wetter than in the drier year. However, the N fertilizer replacement index was higher for subsequent maize grown in the drier year. The cover crop-N recovery in maize was also higher than the urea-N uptake in the drier year. The N fertilizer replacement indexes can be predicted using the above-ground biomass amount of cover crops at 20 weeks after planting (drier year) or the N concentration at that stage (wetter year).