Individuals diagnosed with inflammatory bowel disease (IBD) face a significantly heightened risk of developing colorectal cancer (CRC), primarily due to persistent intestinal inflammation that fosters neoplastic transformations across the colon. This narrative review delves into the potential of certain fruits, such as black raspberries, Amazonian açaí, apples, grapes, cocoa, Ziziphus jujuba, and Moringa oleifera, in mitigating IBD-induced CRC. Preclinical studies indicate that these fruits possess anti-inflammatory and antioxidant properties that may disrupt carcinogenic pathways. Notably, black raspberries have demonstrated the ability to modulate epigenetic markers by demethylating tumor suppressor genes and inhibiting DNA methyltransferases (DNMT), like DNMT1 and DNMT3B. This epigenetic modulation influences the Wnt signaling pathway, crucial in CRC development, and affects cellular processes, such as proliferation, apoptosis, and angiogenesis. Animal models further support these findings, showing that black raspberries can suppress β- catenin signaling, reduce chronic inflammation, and decrease tumor incidence. This comprehensive analysis underscores the promising role of specific fruits in CRC prevention among IBD patients and highlights the need for further research to translate these findings into clinical applications, potentially benefiting both public health and the nutraceutical industry.

Herein, we describe water-soluble heteroaryl azopyridinium ionic photoswitches (HAPIPs). We aim to combine variations in five-membered heterocycles, their substitutions, N-alkyl groups at pyridinium nitrogen, the position of pyridinium center relative to azo group, counterions, and solvents, in achieving better photoswitching. Through these studies, we successfully tuned the half-life of Z isomers of the resultant HAPIPs between seconds to days in water. Extensive spectroscopic studies and density functional theory (DFT) computations unravelled the factors responsible for thermal relaxation behavior. Considering the versatility of these photoswitches, the tunability of half-lives and photoswitching in aqueous medium allows the scope of applications in several fields.

We report the design and synthesis of eight photoswitchable phenylazopyridine- and phenylazopyrazole-based molecular systems as chelation-type light-controllable ligands. Besides the studies on fundamental photoisomerization behaviour, the ligands were also screened for light-tuneable properties such as photochromism, phase transition, and solubility, especially in the aqueous medium. This investigation demonstrates how the modulation of aqueous solubility can be achieved through photoisomerization and can further be utilized towards controlling the amount of catalytically active Cu(I) species in the aqueous conditions. Through this approach, light control over the catalytic activity was achieved for Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reactions, along with a partial recovery of the catalytically active species.

Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

Hypercholesterolemia (HC), a type of dyslipidemia, is one the major causes of metabolic disorders including obesity, diabetes, hypertension, and cardiovascular diseases worldwide. There is vast amount of literature on antihypercholesterolemic effects of statins, COX-2 inhibitors, and other allopathic treatment modalities against dyslipidemia and associated diseases. However, their chronic use is linked to toxicities and unwanted side effects. In this regard, Cannabis due to its unique and beneficial milieu of bioactive components has been known for its antioxidant and antiinflammatory properties. Despite the well-studied ameliorative effects of cannabis on HC through favorably modulating lipid metabolism via maintaining the cholesterol homeostasis and LDL levels, mechanistic details are still limited and inconclusive. This chapter provides a comprehensive review about pathophysiology of HC and highlights the potential role and plausible mechanism(s) of hemp in the management of HC through modulation of lipid metabolism specific and common molecular pathways involving oxidative stress and inflammation.

The paper purposes to describe the spread of Covid-19 in Punjab, pre Covid-19 period, its effects on Punjab Tourism, and also put forwards a set of recovery measures for tourism sector. The data used is secondary in nature, collected from news broadcasted by several media outlets, various journals, newspapers, articles and official website of Punjab Tourism, Ministry of Tourism, WHO. The study investigated that the outbreak of the global pandemic Covid-19 (Corona Virus Disease -2019) pandemic is an unprecedented shock to the state’s tourism industry. The Punjab Tourism was in a prospering state before Covid-19 struck. With the prolonged country-wide lockdown, global economic downturn and associated disruption of movement of tourists, the Punjab tourism industry is facing an extended period of decline. The study indicates the effects of Covid-19 in Punjab Tourism and also extends the preventive measures to tackle the pandemic. Although, the length of the impact will depend upon the duration and gravity of the health crisis, the duration of the lockdown and the manner in which the situation unfolds once the lockdown is lifted yet the situation can be tackled by adopting the suggestive recovery measures. Key words: COVID-19 Pandemic; Punjab Tourism; Tourists Arrival; Spill Over; Recovery Measures.

Rising global temperatures are proving to be detrimental for the agriculture. Hence, strategies are needed to induce thermotolerance in food crops to sustain the food production. GABA (γ-aminobutyric acid), a non-protein amino acid, can partially protect plants from high-temperature stress. This study hypothesises that declining GABA concentrations in the cells of heat-stressed mungbean plants increases the heat-sensitivity of reproductive function. Mungbean plants were grown in a natural, outdoor environment (29.3/16.1 ± 1 °C as mean day/night temperature, 1350–1550 µmol m −2 s −1 light intensity, 60–65% as mean relative humidity) until the start of the reproductive stage. Subsequently, two temperature treatments were imposed in a controlled environment—control (35/23 °C) and heat stress (45/28 °C)—at about 800 µmol m −2 s −1 light intensity and 65–70% as mean relative humidity, until pod maturity. In heat-stressed (HS) plants, endogenous GABA concentrations in leaf and anther samples had declined by 49 and 60%, respectively, and to a much lesser degree in the plants, exogenously supplemented with 1 mM GABA. The reproductive function of GABA-treated heat-stressed plants improved significantly in terms of pollen germination, pollen viability, stigma receptivity and ovule viability, compared to untreated HS controls. In addition, GABA-treated heat-stressed plants had less damage to membranes, photosynthetic machinery (chlorophyll concentration, chlorophyll fluorescence, RuBisCO activity were functionally normal) and carbon assimilation (sucrose synthesis and its utilisation) than the untreated HS controls. Leaf water status improved significantly with GABA application, including enhanced accumulation of osmolytes such as proline and trehalose due to increase in the activities of their biosynthetic enzymes. GABA-treated heat-stressed plants produced more pods (28%) and seed weight (27%) plant −1 than the untreated controls. This study is the first to report the involvement of GABA in protecting reproductive function in mungbean under heat stress, as a result of improved leaf turgor, carbon fixation and assimilation processes, through the augmentation of several enzymes related to these physiological processes.

Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is an immune-modulated disorder characterized by chronic and recurring inflammatory episodes. Oxidative stress and COX pathway of prostaglandin (PG) biosynthesis are indispensable to pathogenesis of UC. Any imbalance between PGs can compromise the mucosal homeostasis, leading to mucosal damage and chronic inflammation. However, blocking these PGs using classical Cox inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs) can instead aggravate signs of IBD. Therefore, realizing the need for safer and well tolerable alterative treatment approaches, currently, we evaluated the efficacy of n-3 fatty acids rich fish oil (FO) in the resolution of UC. Using a dextran sodium sulfate (DSS) model of experimental colitis, we have demonstrated that supplementation of FO containing 180 mg EPA and 120 mg DHA for 1 month relieved the signs (diarrhea, bloody stools, weight loss) of colitis-associated inflammation. To understand the biophysical changes associated with FO mediated inflammatory regulation, impedance measurement and Fourier transform infrared spectroscopy (FTIR) were done. These changes were also correlated with oxidative stress through markers such as GST, glutathione peroxidase (GPx), LPO, catalase, protein carbonyl content, GR, etc. in colonic mucosa. The modulation of COX mediated pathways in UC-associated inflammation was observed by protein expressions of various pro-inflammatory cytokines such as TNF-α and enzymes of PG synthesis such as COX-2, PGES, TXAS, and anti-inflammatory PGDS. Refuting the earlier reports that suggested the contradictory effects of FO, in the current study, we evidently demonstrated that the protective effects of FO are mediated through molecular mechanisms involving the redox-regulation of metabolism of key lipid metabolites.

The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid–based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis–like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies proved that SLN-encapsulated MTA can be substantially delivered to the brain and can effectively remyelinate the neurons. It can reverse the multiple sclerosis–like symptoms in a safer and effective manner, that too by oral route.

With the intention of producing the most comprehensive treatment of the prevalence of crystal polymorphism among structurally characterized materials, all polymorphic compounds flagged as such within the Cambridge Structural Database (CSD) are analysed and a list of crystallographically characterized organic polymorphic compounds is assembled. Classifying these structures into subclasses of anhydrates, salts, hydrates, non-hydrated solvates and cocrystals reveals that there are significant variations in polymorphism prevalence as a function of crystal type, a fact which has not previously been recognized in the literature. It is also shown that, as a percentage, polymorphic entries are decreasing temporally within the CSD, with the notable exception of cocrystals, which continue to rise at a rate that is a constant fraction of the overall entries. Some phenomena identified that require additional scrutiny include the relative prevalence of temperature-induced phase transitions among organic salts and the paucity of polymorphism in crystals with three or more chemical components.

Crystal form screening of the antiepileptic drug Retigabine was undertaken to establish the stability order among the known trimorphs and design new cocrystals of the drug. X-ray crystal structures of polymorphs A and B have been determined, and the thermodynamic stability among the trimorphs at ambient conditions was found to be in the order B (least stable) < C < A (most stable) from thermal and phase transformation experiments. Two anhydrous cocrystals, an anhydrous salt and a eutectic of Retigabine were successfully designed and characterized. Interestingly, Retigabine forms a cocrystal with 4-hydroxybenzoic acid only with a water of crystallization (i.e., as a cocrystal hydrate), or else the binary combination manifests as a eutectic. The number of hydroxyl groups and water is implicated in the formation of anhydrous/hydrated cocrystals and eutectic respectively among the combinations explored.

UC a form of IBD is a chronic inflammatory disorder of large intestine, with unknown etiology. Reports suggest a critical role of COX-2 dependent prostaglandins (PGs) mediated inflammatory pathway in pathophysiology of UC. However, COX inhibition using NSAIDs exacerbate IBD and thus is not a viable solution. Currently, in DSS induced experimental colitis in mice, we have demonstrated that dietary Se supplementation (0.5ppm as sodium selenite) symptomatically resolves the signs of inflammation in a redox sensitive manner as compared to Se deficient (0.01ppm) conditions, as seen by modulation in oxidative stress markers, morphological changes, histopathological examinations, biochemical studies such as MPO activity, activity of intestinal markers enzymes as well as mRNA and expressions of various pro and anti-inflammatory factors such as, mPGES, hPGDS, TXAS, 15-PGDH, GPX-1 and GPX-2. These findings were validated and correlated with changes in the biophysical parameters such as membrane fluidity, electrical parameters (impedance), transport across the colonic tissue and FTIR. Current study not only concluded that Se at supranutritional concentrations by modulating the redox status relieves the signs of colitis by regulating COX dependent PG biosynthetic pathway, but also sheds light on the biophysical characterization of these inflammatory/resolution pathways involved in UC.

Multiple sclerosis (MS) is a neurodegenerative disease in which myelin sheath damage occurs due to internal and external factors. MS especially affects the young population. Dimethyl fumarate (DMF) is a promising agent for MS treatment, although it is associated with concerns such as poor brain permeation, multiple dosing, and gastrointestinal flushing. The present study attempts to evaluate the preclinical performance of specially designed DMF-based lipoidal nanoparticles in a cuprizone-induced demyelination model in rodents. The studies proved the efficacy of lipid-based nanoparticles containing DMF in a once-a-day dosage regimen over that of thrice-a-day plain DMF administration on crucial parameters like motor coordination, grip strength, mortality, body weight, and locomotor activity. However, neither blank lipid nor blank neuroprotective (vitamins A, D, and E) loaded nanoparticles were able to elicit any desirable behavioral response. Histopathological studies showed that the designed once-a-day DMF nanomedicines were well tolerated and rejuvenated the myelin sheath vis-à-vis the plain DMF thrice-a-day regimen. These findings provide proof of concept for a biocompatible nanomedicine for MS with tremendous promise for effective brain delivery and patient compliance on the grounds of a reduction in the dosage frequency.

Epilepsy is a common neurological disorder observed in an estimated prevalence of 1% of the world’s population. The therapeutic strategy in treating epilepsy involves reducing neuronal excitability. Retigabine (RTG) has been developed as an orally active, neuronal potassium channel opener and with its low solubility and high permeability is identified as a class II drug under the Biopharmaceutics Classification System (BCS) as a water insoluble drug. Hence, enhancing the aqueous solubility is crucial for the dosage to be minimized thus enhancing both clinical (reducing side effects) and commercial aspects. We have approached this issue in terms of polymorphism, cocrystallization adducts including salts, cocrystals and eutectics of RTG. Retigabine exists in three polymorphic forms, two are determined from single crystal X-ray diffraction studies, The third form is less stable and readily converts to the most stable form A. Further, thermal and seeding experiments are performed to determine the stability order among the three polymorphs. Co-cocrystallization of RTG results in a nitrate salt, cocrystal of hydroxy substituted benzoic acids, a eutectic with benzoic acid and the structural aspects of these water soluble adducts have been analysed.

The purpose of this paper is to study what determines the health seeking behaviour among the poor and further, whether the insurance coverage differs in seeking the treatment. The authors adopted descriptive study by using a semi-structured questionnaire canvassed among 227 low income households in rural and urban settings of Jalandhar, Amritsar and Moga districts of Punjab. The major results are that the insurance coverage has significant influence on the type of treatment preferred by the low-income households. The households belonging to the rural area and no insurance coverage preferred to take the treatment following home remedies and visit to clinic near the home. However, government hospitals are also preferred when the number of dependents are more than three and have no insurance coverage. The analysis reveals that the health insurance coverage for the low-income people supports them for a better-quality healthcare at affordable cost.

We present near-infrared (NIR) imaging observations of three transient neutron star X-ray binaries, SAX J1753.5-2349, SAX J1806.5-2215 and AX J1754.2-2754. All three sources are members of the class of ` very faint' X-ray transients which exhibit X-ray luminosities L-X less than or similar to 10(36) erg s(-1). The nature of this class of sources is still poorly understood. We detect NIR counterparts for all three systems and perform multiband photometry for both SAX J1753.52349 andSAXJ1806.5-2215, including narrow-band Br gamma photometry for SAXJ1806.5-2215. We find that SAX J1753.5-2349 is significantly redder than the field population, indicating that there may be absorption intrinsic to the system, or perhaps a jet is contributing to the infrared emission. SAX J1806.5-2215 appears to exhibit absorption in Br gamma providing evidence for hydrogen in the system. Our observations of AX J1754.2-2754 represent the first detection of an NIR counterpart for this system. We find that none of the measured magnitudes are consistent with the expected quiescent magnitudes of these systems. Assuming that the infrared radiation is dominated by either the disc or the companion star, the observed magnitudes argue against an ultracompact nature for all three systems.

A drug-drug cocrystal of two anticonvulsants, lamotrigine and phenobarbital, is presented. In the crystal structure, molecules form heterodimers via N-H···O and N-H···N hydrogen bonding. The intrinsic dissolution rate (IDR) and solubility of the cocrystal were measured in phosphate buffer (pH 7.2) and simulated gastric fluid (without pepsin), and compared to pure APIs. Dissolution experiments found suppressed IDR of the cocrystal with rates in the order pure PB > pure LTG > cocrystal. The solubility measurements were consistent with the dissolution behavior. The presence of strong heterodimers in the cocrystal compared to weaker homodimers in the parent drugs is implicated for the reduced solubility and dissolution rate.

Epilepsy is a common neurological disorder observed in an estimated prevalence of 1% of the world’s population. The therapeutic strategy in treating epilepsy involves reducing neuronal excitability. Retigabine (RTG) has been developed as an orally active, neuronal potassium channel opener and with its low solubility and high permeability is identified as a class II drug under the Biopharmaceutics Classification System (BCS) as a water insoluble drug. Hence, enhancing the aqueous solubility is crucial for the dosage to be minimized thus enhancing both clinical (reducing side effects) and commercial aspects. We have approached this issue in terms of polymorphism, cocrystallization adducts including salts, cocrystals and eutectics of RTG. Retigabine exists in three polymorphic forms, two are determined from single crystal X-ray diffraction studies, The third form is less stable and readily converts to the most stable form A. Further, thermal and seeding experiments are performed to determine the stability order among the three polymorphs. Co-cocrystallization of RTG results in a nitrate salt, cocrystal of hydroxy substituted benzoic acids, a eutectic with benzoic acid and the structural aspects of these water soluble adducts have been analysed. [ 1 ] Hopkins, C. R. (2012). ACS Chem. Neurosci. 3, 632-632. [ 2 ] Takagi, T. et al. (2006). Mol. Pharm. 3, 631-643. [ 3 ] Schultheiss, N. & Newman, A. (2009). Cryst. Growth Des. 9, 2950-2967.

One of the key challenges of fuel cell technology is to find solid electrolytes which are cheap and environmentally friendly with high proton (H+) conductivities. In this context, designing new materials based on organic cocrystals/salts appears very promising to expand the scope of H+ ion conductors. In our approach, we have synthesized a quaternary organic salt consisting of gallic acid, isoniazid, sulfate (SO42-) ion, and water by a slow evaporation method which exhibits high proton conductivity of 0.2 mS cm(-1) at 293 K to serve as a model system. The proton conductivity value observed in our system is comparable and in some cases better than recently published coordination polymers, metal organic frameworks, and covalent organic frameworks. The system crystallizes as monoclinic with space group P2(1)/c (Z' = 3; Z = 12), which depicts a layered structure with extensive O-H center dot center dot center dot O and N-H center dot center dot center dot O hydrogen bonding networks. Further, it exhibits interesting order-disorder phase transitions at both high and low temperatures. Calculation of the activation energy (similar to 0.39 eV) from conductivity plots for the system reveals the mechanism of proton conduction to be Grotthuss type. Thus, our novel design strategy of preparing an organic salt for proton conduction applications opens up a pathway to generate easy synthesis of cheap and environmentally friendly materials.

We present our near-infrared (NIR) imaging observations of two neutron star low-mass X-ray binaries XMMU J174716.1−281048 and SAX J1806.5−2215 obtained using the PANIC instrument on the 6.5-metre Magellan telescope and the WIYN High-Resolution Infrared Camera instrument on the 3.5-metre WIYN telescope, respectively. Both sources are members of the class of faint to very faint X-ray binaries and undergo very long X-ray outburst, hence classified as ‘quasi-persistent X-ray binaries’. While XMMU J174716.1−281048 was active for almost 12 yr between 2003 and 2015, SAX J1806.5−2215 has been active for more than 5 yr now since 2011. From our observations, we identify two NIR stars consistent with the Chandra X-ray error circle of XMMU J174716.1−281048. The comparison of our observations with the United Kingdom Infrared Telescope (UKIRT) Galactic plane observations taken during the same outburst, colour–colour diagram analysis and spectral energy distribution suggest that both stars are probably a part of the field population and are likely high-mass stars. Hence possibly neither of the two stars is a true NIR counterpart. For the faint X-ray binary SAX J1806.5−2215 during its current outburst, we detected an NIR star in our K-band WIYN observations consistent with its Chandra error circle. The identified NIR star was not detected during the UKIRT observations taken during its quiescent state. The comparison of two observations suggests that there was an increase in flux by at least one magnitude of the detected star during our observations, and hence suggests the detection of the likely counterpart of SAX J1806.5−2215.