Dynamic Metal-Coordinated Adhesive and Self-Healable Antifreezing Hydrogels for Strain Sensing, Flexible Supercapacitors, and EMI Shielding Applications.

Dynamic metal-coordinated adhesive and self-healable hydrogel materials have garnered significant attention in recent years due to their potential applications in various fields. These hydrogels can form reversible metal-ligand bonds, resulting in a network structure that can be easily broken and reformed, leading to self-healing capabilities. In addition, these hydrogels possess excellent mechanical strength and flexibility, making them suitable for strain-sensing applications. In this work, we have developed a mechanically robust, highly stretchable, self-healing, and adhesive hydrogel by incorporating Ca2+-dicarboxylate dynamic metal-ligand cross-links in combination with low density chemical cross-links into a poly(acrylamide-co-maleic acid) copolymer structure. Utilizing the reversible nature of the Ca2+-dicarboxylate bond, the hydrogel exhibited a tensile strength of up to ∼250 kPa and was able to stretch to 15-16 times its original length. The hydrogel exhibited a high fracture energy of ∼1500 J m-2, similar to that of cartilage. Furthermore, the hydrogel showed good recovery, fatigue resistance, and fast self-healing properties due to the reversible Ca2+-dicarboxylate cross-links. The presence of Ca2+ resulted in a highly conductive hydrogel, which was utilized to design a flexible resistive strain sensor. This hydrogel can strongly adhere to different substrates, making it advantageous for applications in flexible electronic devices. When adhered to human body parts, the hydrogel can efficiently detect limb movements. The hydrogel also exhibited excellent performance as a solid electrolyte for flexible supercapacitors, with a capacitance of ∼260 F/g at 0.5 A/g current density. Due to its antifreezing and antidehydration properties, this hydrogel retains its flexibility at subzero temperatures for an extended period. Additionally, the porous network and high water content of the hydrogel impart remarkable electromagnetic attenuation properties, with a value of ∼38 dB in the 14.5-20.5 GHz frequency range, which is higher than any other hydrogel without conducting fillers. Overall, the hydrogel reported in this study exhibits diverse applications as a strain sensor, solid electrolyte for flexible supercapacitors, and efficient material for electromagnetic attenuation. Its multifunctional properties make it a promising candidate for use in various fields as a state-of-the-art material.

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6-8 weeks old healthy infants: A phase III, randomized, single blind, non-inferiority study.

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.

Role of dexmedetomidine as an anaesthetic adjuvant in breast cancer surgery as a day-care procedure: A randomised controlled study.

BACKGROUND AND AIMS: Breast cancer surgery can be carried out as day-care procedure to increase patient turnover, decrease disease progression and financial burden. The present study was carried out to assess the role of dexmedetomidine in breast cancer surgery as a day-care procedure. METHODS: This prospective randomised, double-blind study was carried out on 100 patients screened for day-care breast cancer surgery. They were divided into two groups of 50 each; who received either normal saline (Group NS) or 0.6 µg/kg/h dexmedetomidine (Group D) infusion from 10 min before induction until skin closure. All patients were given general anaesthesia. The incidence of discharge, post-operative pain (POP), average rescue analgesia (fentanyl) required and side effects were noted. Statistical analysis was performed using Student's t-test and Chi-square test. RESULTS: Incidence of discharge in group NS was 60% compared to 88% in Group D (P = 0.001). Average rescue analgesia requirement by group NS was 136.07 ± 43.06 µg, whereas it was 77.5 ± 29.86 µg in Group D (P = 0.01). The incidence of POP in 6 h and within 2 h of expected discharge time in Group NS was 56% and 28%, respectively, and in Group D, it was 8% in both the periods (P < 0.001 and 0.01). Side effects such as post-operative nausea, vomiting and bleeding were encountered in eight and two patients, respectively, in Group NS and two and one patients, respectively, in Group D. CONCLUSION: Dexmedetomidine as an anaesthetic adjuvant makes breast cancer surgery feasible on day-care basis.

Analysis of muscle activation in lower extremity for static balance.

Balance plays an important role for human bipedal locomotion. Degeneration of balance control is prominent in stroke patients, elderly adults and even for majority of obese people. Design of personalized balance training program, in order to strengthen muscles, requires the analysis of muscle activation during an activity. In this paper we have proposed an affordable and portable approach to analyze the relationship between the static balance strategy and activation of various lower extremity muscles. To do that we have considered Microsoft Kinect XBox 360 as a motion sensing device and Wii balance board for measuring external force information. For analyzing the muscle activation pattern related to static balance, participants are asked to do the single limb stance (SLS) exercise on the balance board and in front of the Kinect. Static optimization to minimize the overall muscle activation pattern is carried out using OpenSim, which is an open-source musculoskeletal simulation software. The study is done on ten normal and ten obese people, grouped according to body mass index (BMI). Results suggest that the lower extremity muscles like biceps femoris, psoas major, sartorius, iliacus play the major role for both maintaining the balance using one limb as well as maintaining the flexion of the other limb during SLS. Further investigations reveal that the higher muscle activations of the flexed leg for normal group demonstrate higher strength. Moreover, the lower muscle activation of the standing leg for normal group demonstrate more headroom for the biceps femoris-short-head and psoas major to withstand the load and hence have better static balance control.

Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate.

Perinatal exposure of rats and mice to the typically reported 4mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform--all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2mg/g bd wt on alternate days for the first 9days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70-80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible.

Irreversible perinatal imprinting of adult expression of the principal sex-dependent drug-metabolizing enzyme CYP2C11.

We proposed to determine whether, like other sexual dimorphisms, drug metabolism is permanently imprinted by perinatal hormones, resulting in its irreversible sex-dependent expression. We treated newborn male rats with monosodium glutamate (MSG), a total growth hormone (GH) blocker, and, using cultured hepatocytes, examined expression of adult CYP2C11, the predominant cytochrome-P450 expressed only in males, as well as the signal transduction pathway by which episodic GH solely regulates the isoform's expression. In addition, adolescent hypophysectomized (hypox) male rats served as controls in which GH was eliminated after the critical imprinting period. Whereas renaturalization of the masculine episodic GH profile restored normal male-like levels of CYP2C11, as well as CYP2C12, in hepatocytes from hypox rats, the cells derived from the MSG-treated rats were completely unresponsive. Moreover, GH exposure of hepatocytes from hypox rats resulted in normal induction, activation, nuclear translocation, and binding to the CYP2C11 promoter of the signal transducers mediating GH regulation of CYP2C11 expression, which dramatically contrasted with the complete unresponsiveness of the MSG-derived hepatocytes, also associated with hypermethylation of GH-response elements in the CYP2C11 promoter. Lastly, neonatal MSG treatment had no adverse effect on postnatal and adult testosterone levels. The results demonstrate that the sexually dimorphic expression of CYP2C11 is irreversibly imprinted shortly after birth by a hormone other than the customary testosterone, but likely by GH.

Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice.

BACKGROUND & OBJECTIVES: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. METHODS: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 µg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. RESULTS: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. INTERPRETATION & CONCLUSIONS: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action.

Growth hormone-independent suppression of growth hormone-dependent female isoforms of cytochrome P450 by the somatostatin analog octreotide.

Octreotide is a potent somatostatin analog therapeutically used to treat several conditions including hyper growth hormone secretion in patients with acromegaly. We infused octreotide into female Sprague Dawley rats every 12h for 6 days at levels considerably greater than typical human therapeutic doses. Resulting circulating growth hormone profiles were characterized by ∼25% reduction in plasma levels, including both pulse and interpulse components, but still contained in an otherwise female-like "continuous" secretory profile. The normally elevated feminine expression levels (protein and/or mRNA) of CYP2C12, CYP2A1, CYP2C7 and insulin-like growth factor-1 (IGF-1), all dependent on the continuous feminine growth hormone profile, were dramatically down-regulated. Octreotide suppression of the female-dependent levels of CYPs (cytochromes P450) and IGF-1 could not be explained by the apparently inconsequential alterations in the feminine circulating growth hormone profile. In this regard, somatostatin and its analogs are known to have a myriad of extra-pituitary actions effecting nearly all tissues in the body. Focusing our attention on CYP2C12, accounting for >40% of the total hepatic cytochrome P450 content in the female rat liver, we found a ∼4-fold increase in hepatic ubiquitin-CYP2C12 levels in octreotide treated rats suggesting a possible contributing factor for the >60% suppression of CYP2C12 protein concentrations.

Noncanonical suppression of GH-dependent isoforms of cytochrome P450 by the somatostatin analog octreotide.

Octreotide is a potent somatostatin analog therapeutically used to treat several conditions including hyper GH secretion in patients with acromegaly. We infused, over 30 s, octreotide into male rats every 12 h for 6 days at levels considerably greater than typical human therapeutic doses. Unexpectedly, resulting circulating GH profile was characterized by pulses of higher amplitudes, longer durations, and greater total content than normal, but still contained an otherwise male-like episodic secretory profiles. In apparent disaccord, the normally elevated masculine expression levels (protein and/or mRNA) of CYP2C11 (accounting for >50% of the total hepatic cytochrome P450 content), CYP3A2, CYP2C7, and IGF1, dependent on the episodic GH profile, were considerably downregulated. We explain this contradiction by proposing that the requisite minimal GH-devoid interpulse durations in the masculine profile that solely regulate expression of at least CYP2C11 and IGF1 may be sufficiently reduced to suppress transcription of the hepatic genes. Alternatively, we observed that octreotide infusion may have acted directly on the hepatocytes to induce expression of immune response factors postulated to suppress CYP transcription and/or upregulate expression of several negative regulators (e.g. phosphatases and SOCS proteins) of the JAK2/STAT5B signaling pathway that normally mediates the upregulation of CYP2C11 and IGF1 by the masculine episodic GH profile.

Protective effect of diphenylmethyl selenocyanate against CCl4-induced hepatic injury.

Organoselenocyanates represent an important class of chemopreventive agent, which possess antioxidative, antimutagenic as well as cancer chemopreventive properties. The present study is an attempt to evaluate the protective effect of diphenylmethyl selenocyanate -- a synthetic organoselenocyanate against carbon tetrachloride (CCl(4))-induced hepatic damage in Swiss albino mice in vivo. Mice were pretreated with the Se-compound orally in a duration dependent manner (7 and 15 days) to observe its protective action against an acute toxic dose (24 h) of CCl(4) (single injection at a dose of 20 microl and 50 microl kg(-1) b.w.) that induced hepatic necrosis and caused DNA damage (strand breaks) in the hepatocytes. This study revealed that pretreatment with the Se-compound reduced the extent of massive hepatic necrosis in a duration dependent manner, but it had no modulatory effect on hepatocellular apoptosis caused by acute toxic doses of CCl(4). It was also found that the Se-compound could significantly (P < 0.01) prevent the CCl(4)-induced elevation of DNA damage in hepatocytes measured by comet assay in a duration dependent manner. So these findings will further strengthen the view that organoselenocyanate is an effective chemopreventive agent against acute hepatic damage, caused by halogenated alkanes such as CCl(4).

Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways.

Chemoprevention of colorectal cancer has become essential in the modern industrialized world as cancer of the large bowel has become one of the major causes of cancer mortality, second only to lung cancer. Colon cancer integrates lifestyle factors and multistep genetic alterations, and without preventive intervention, a substantial part of the population is likely to develop colorectal cancer at some point during their lives. Diet and nutrition clearly play a role in the etiology of colon cancer. Inhibitory activity of aqueous suspensions of garlic, tomato and black tea was tested on azoxymethane-induced colon carcinogenesis in Sprague-Dawley rats during earlier studies. In the present study, the protective activity of diallylsulfide and lycopene and theaflavin, important antioxidative ingredients of garlic, tomato and black tea, respectively, was assessed during colon carcinogenesis. The effect was observed on aberrant crypt foci, the preneoplastic lesion. As inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activities is correlated with the prevention of colon cancer, the study continues with the determination of the change in the expression of these proteins. Following treatment, significant reduction in the incidences of aberrant crypt foci (by 43.65% in diallylsulfide, 57.39% in lycopene and 66.08% in theaflavin group) was observed, which was in accordance with the reduced expression of cyclooxygenase-2 and inducible nitric oxide synthase. The effect of the intact source was found to be more pronounced than their components used separately.

Diphenylmethyl selenocyanate inhibits DMBA-croton oil induced two-stage mouse skin carcinogenesis by inducing apoptosis and inhibiting cutaneous cell proliferation.

Numerous epidemiological and experimental studies have showed the inverse relationship between dietary selenium intake and different types of cancer. Continuous efforts are going on to develop suitable organoselenium compounds, which can be used as cancer chemopreventive agents for human. In the present study, a synthetic organoselenium compound diphenylmethyl selenocyanate was evaluated for its ability to arrest cell proliferation and to induce apoptosis against 7,12-dimethylbenz[a]anthracene-croton oil induced two-stage mouse skin carcinogenesis model. Reduction in the incidence and number of papilloma, the preneoplastic lesion, was considered to be the mean of assessment. Significant decrease in the level of cell proliferation (p<0.01) and significant enhancement in the level of apoptosis (p<0.01) were found. Caspase-3, which contribute a part in the process of cellular apoptosis to prevent further cellular differentiation was also elevated significantly (P<0.01) during the treatment with the Se compound. These observations seem to be correlated with the significant reduction in the corresponding number of skin papilloma formation after 12 weeks of experiment. Thus the compound, diphenylmethyl selenocyanate may be considered for further research to establish it as an effective cancer chemopreventive agent.

Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy.

Inhibition of azoxymethane-induced aberrant crypt foci in rat by diphenylmethyl selenocyanate through downregulation of COX-2 and modulation of glutathione-S-transferase and lipid peroxidation.

Preventive intervention of colorectal cancer has become essential, as a major portion of the population could develop the disease at some point during their lives. An inverse association between dietary intake of selenium, an important biological trace element, and colorectal cancer risk has been observed through epidemiological and experimental studies. Inhibitory activity of an organoselenocyanate, diphenylmethylselenocyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcinogenesis in Sprague-Dawley rats. Pretreatment and concomitant treatment, at a dose of 2 mg/kg body wt, was carried out and the effect was observed on aberrant crypt foci, the preneoplastic lesion. To investigate the mechanism of action of the compound, lipid peroxidation level and glutathione-S-transferase (GST) activities were assessed in the liver as well as in the colon. Expression of cyclooxygenase-2 protein, inducible during colon carcinogenesis, was also analyzed in the colon. Inhibitory activity of the compound was shown by the reduced incidences of aberrant crypt foci in the treated groups (by 63.3%, p=0.00044 in the pretreated group, and by 44%, p=0.0067 in the concomitant treatment group). Significant induction of GST activities and significant reduction in lipid peroxidation level both in the liver as well as in the colon and suppression of cyclooxygenase-2 expression in the colon of the treated groups suggest that the compound could exert its preventive effect at different levels of the carcinogenic process. The preventive effect was better in the pretreatment group than in the concomitant treatment group, suggesting some added protection to the target tissue resulting from preadministration of the compound.

Protective effect of diphenylmethyl selenocyanate against carbon tetrachloride-induced hepatotoxicity in vivo.

Carbon tetrachloride (CCl(4)) is a known hepatotoxic compound working through the generation of reactive free radicals. Selenium (Se) is an essential trace element required by animals and humans for protection against xenobiotic compounds. In this study, Se, as diphenylmethyl selenocyanate, has been evaluated for its protective action against CCl(4)-induced hepatotoxicity in Swiss albino mice. Treatment with Se compound was found to upregulate different phase II detoxifying enzymes (catalase, superoxide dismutases, reduced glutathione, and glutathione transferase) in liver of mice challenged with different doses of CCl(4) as compared to the CCl(4) control, when measured after 24 hours of CCl(4) treatment (p < 0.01). The Se compound also significantly (p < 0.01) inhibited the level of membrane lipid peroxidation and serum transferase activity (ALT and AST) in the treated group as compared to the control group.

Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and inhibition of nitric oxide production.

Selenium, an essential micronutrient, plays important roles against different diseases, including several types of cancer. In the present study, antioxidative and chemopreventive properties of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a) anthracene - croton oil induced two-stage mouse skin carcinogenesis model. The compound was administered orally to carcinogen-treated mice at two different non-toxic doses, 2mg/kg. b.w. and 3mg/kg. b.w. Significant inhibition in the incidence of papilloma formation (53-80%) as well as in the cumulative numbers of papillomas per papilloma bearing mouse were observed in the treated groups as compared to the carcinogen control group. The compound was also found to upregulate significantly different phase II detoxifying enzymes such as glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin cytosol when measured after 15 days and also after 12 weeks of the first 7,12-dimethylbenz (a) anthracene treatment. Lipid peroxidation measured with reference to thiobarbituric acid reactive substances in skin microsomes was significantly inhibited (p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate. Considerable inhibition of the level of nitric oxide production in peritoneal macrophages was observed after 12 weeks (p<0.05). Thus the compound appears to exert chemopreventive activity in terms of papilloma formation, which may be through modulation of cutaneous lipid peroxidation, the phase II detoxifying enzyme system and nitric oxide production.