Effect of salinity stress on organic and mineral constituents in the leaves of pigeonpea (Cajanus cajan L. Var. C-11)

Summary Effects of sodium chloride and sodium sulphate on the content of some organic and inorganic constituents in the leaves of pigeonpea (Cajanus cajan L. Var. C-11) were studied. Increased water content under saline conditions made the leaves succulent. The concentration of reducing sugars appeared to be higher while that of total sugars and starch was lower. The plants also failed to accumulate proline at higher salinity levels. Phosphorus and potassium content were lowered while those of calcium, magnesium, sodium, chloride and sulphate were increase under both salinities. This indicates that there is no regulation on the uptake of latter elements under saline conditions.     

Purification, properties and alternate substrate specificities of arginase from two different sources: Vigna catjang cotyledon and buffalo liver

Arginase was purified from Vigna catjang cotyledons and buffalo liver by chromatographic separations using Bio-Gel P-150, DEAE-cellulose and arginine AH Sepharose 4B affinity columns. The native molecular weight of an enzyme estimated on Bio-Gel P-300 column for Vigna catjang was 210 kDa and 120 kDa of buffalo liver, while SDS-PAGE showed a single band of molecular weight 52 kDa for cotyledon and 43 kDa for buffalo liver arginase. The kinetic properties determined for the purified cotyledon and liver arginase showed an optimum pH of 10.0 and pH 9.2 respectively. Optimal cofactor Mn++ ion concentration was found to be 0.6 mM for cotyledon and 2 mM for liver arginase. The Michaelis-Menten constant for cotyledon arginase and hepatic arginase were found to be 42 mM and 2 mM respectively. The activity of guanidino compounds as alternate substrates for Vigna catjang cotyledon and buffalo liver arginase is critically dependent on the length of the amino acid side chain and the number of carbon atoms. In addition to L-arginine cotyledon arginase showed substrate specificity towards agmatine and L-canavanine, whereas the liver arginase showed substrate specificity towards only L-canavanine.     

Soft drug-resistant ovarian cancer cells migrate via two distinct mechanisms utilizing myosin II-based contractility

The failure of chemotherapeutic drugs in treatment of various cancers is attributed to the acquisition of drug resistance. However, the migration mechanisms of drug-resistant cancer cells remain incompletely understood. Here we address this question from a biophysical perspective by mapping the phenotypic alterations in ovarian cancer cells (OCCs) resistant to cisplatin and paclitaxel. We show that cisplatin-resistant (CisR), paclitaxel-resistant (PacR) and dual drug-resistant (i.e., resistant to both drugs) OCCs are more contractile and softer than drug-sensitive cells. Protease inhibition suppresses invasion of CisR cells but not of PacR cells, indicative of a protease-dependent mode of migration in CisR cells and a protease-independent mode of migration in PacR. Despite these differences, actomyosin contractility, mediated by the RhoA-ROCK2-Myosin II signaling pathway, regulates both modes of migration. Confined migration experiments establish the role of myosin IIA and IIB in mediating nuclear translocation and regulation of proteolytic activity. Collectively, our results highlight the importance of myosin II as a potential therapeutic target for treatment of drug-resistant ovarian cancer cells.     

From Bench to Humans: Formulation Development of a Poorly Water Soluble Drug to Mitigate Food Effect

This study presents a formulation approach that was shown to mitigate the dramatic food effect observed for a BCS Class II drug. In vitro (dissolution), in vivo (dog), and in silico (GastroPlus®) models were developed to understand the food effect and design strategies to mitigate it. The results showed that such models can be used successfully to mimic the clinically observed food effect. GastroPlus® modeling showed that food effect was primarily due to the extensive solubilization of the drug into the dietary lipid content of the meal. Several formulations were screened for dissolution rate using the biorelevant dissolution tests. Surfactant type and binder amount were found to play a significant role in the dissolution rate of the tablet prototypes that were manufactured using a high-shear wet granulation process. The performance of the lead prototypes (exhibiting best in vitro dissolution performance) was tested in dogs and human subjects. A new formulation approach, where vitamin E TPGS was included in the tablet formulation, was found to mitigate the food effect in humans.     

Influence of Process Parameters on Tablet Bed Microenvironmental Factors During Pan Coating

Recent studies have shown the importance of monitoring microenvironmental conditions (temperature, relative humidity) experienced by the tablet bed during a pan coating process, thereby necessitating the need to understand how various process parameters influence these microenvironmental conditions. The process parameters studied in this work include exhaust air temperature, spray rate, inlet airflow rate, gun-to-bed distance, coating suspension percent solids, and atomization and pattern air pressure. Each of these process parameters was found to have an impact on the tablet bed relative humidity (RH), as measured using PyroButton data logging devices. A higher tablet bed RH was obtained with an increase in spray rate and atomization air pressure and with a decrease in exhaust air temperature, inlet airflow rate, gun-to-bed distance, suspension percent solids, and pattern air pressure. Based on this work, it can be concluded that the tablet bed thermodynamic conditions are a cumulative effect of the various process conditions. A strong correlation between the tablet bed RH and the frequency of tablet coating defect (logo bridging) was established, with increasing RH resulting in a higher percent of logo bridging events.     

The kinetics of inhibition of Vigna catjang cotyledon and buffalo liver arginase by L-proline and branched-chain amino acids

The effect of proline, isoleucine, leucine, valine, lysine and ornithine under standard physiological conditions, on purified Vigna catjang cotyledon and buffalo liver arginases was studied. The results showed that V. catjang cotyledon arginase is inhibited by proline at a lower concentration than buffalo liver arginase and the inhibition was found to be linear competitive for both enzymes. Buffalo liver arginase was more sensitive to inhibition by branched-chain amino acids than V. catjang cotyledon. Leucine, lysine, ornithine and valine are competitive inhibitors while isoleucine is a mixed type of inhibitor of liver arginase. We have also studied the effect of manganese concentration which acts as a cofactor and leads to activation of arginase. The optimum Mn2+ concentration for Vigna catjang cotyledon arginase is 0.6 mM and liver arginase is 2.0 mM. The preincubation period required for liver arginase is 20 min at 55 degrees C, the preincubation period and temperature required for activation of cotyledon arginase was found to be 8 min at 35 degrees C. The function of cotyledon arginase in polyamine biosynthesis and a possible role of branched chain amino acids in hydrolysis of arginine in liver are discussed.     

Injuries causing major loss of scalp

Long hair worn by both sexes in a majority of the rural population of Punjab (India) increases the hazard of descalping injuries. Forty-six cases seen over a period of 10 years are reported. Agricultural machinery accounted for 83 percent of these injuries. Males were most commonly involved (63 percent), and 48 percent of the patients were minors. Nearly all cases reported had at least half the scalp avulsed, 56.5 percent being total scalp avulsions, with bare bone exposed in 48 percent of the total. The method of chiseling the outer portion of the exposed bone down to bleeding points and immediately applying a split-thickness skin graft is presented as the procedure of choice for wound closure. This reduced the average hospitalization period by 49 percent as compared with older methods. Follow-up of 67 percent of patients has revealed a surprising instability of the grafted skin, with an ultimate danger of malignant degeneration.     

A microbial metabolite remodels the gut-liver axis following bariatric surgery

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Capsule development and structural characterization of acidic extracellular polysaccharides secreted by cowpea Rhizobia

Capsular development and detailed morphology of exostructures of cowpeaRhizobium sp. JLn(c) were examined by transmission electron microscopy. The capsule development began at one pole in the form of polar fibrils in the early-exponential phase and extended further to cover the cell completely at the mid-exponential phase. Exostructures excreted by cowpeaRhizobium sp. JLn(c) have been found to be attached to cells or free in the culture medium; they consisted of mixtures of complex acidic exopolysaccharides (Type I) and neutral glucans (Type II). These polymers were separated by gel filtration and high-pressure liquid chromatography. The acidic microfibrils from JLn(c) were isolated and identified as cellulose by infrared spectral analysis. This acidic polymer was chemically characterized and was found to contain mainly glucose, galactose, glucuronic acid, mannose, fucose, pyruvate, acetate, and uronates.     

Effects of photobiomodulation on bone defects grafted with bone substitutes: A systematic review of in vivo animal studies

A present, photobiomodulation therapy (PBMT) effectiveness in enhancing bone regeneration in bone defects grafted with or without biomaterials is unclear. This systematic review (PROSPERO, ref. CRD 42019148959) aimed to critically appraise animal in vivo published data and present the efficacy of PBMT and its potential synergistic effects on grafted bone defects. MEDLINE, CCCT, Scopus, Science Direct, Google Scholar, EMBASE, EBSCO were searched, utilizing the following keywords: bone repair; low-level laser therapy; LLLT; light emitting diode; LEDs; photobiomodulation therapy; in vivo animal studies, bone substitutes, to identify studies between 1994 and 2019. After applying the eligibility criteria, 38 papers included where the results reported according to “PRISMA.” The results revealed insufficient and incomplete PBM parameters, however, the outcomes with or without biomaterials have positive effects on bone healing. In conclusion, in vivo animal studies with a standardized protocol to elucidate the effects of PBMT on biomaterials are required initially prior to clinical studies.