Azopyridinium Ionic Photoswitches: Tuning Half-lives of Z Isomers from Seconds to Days in Water.

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.

Photoswitchable Azoheteroarene-Based Chelating Ligands: Light Modulation of Properties, Aqueous Solubility and Catalysis.

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.

Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis.

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.

Seroprevalence of measles, mumps & rubella antibodies among 5-10 years old children in north India.

Background & objectives: : Globally, there is an effort to eliminate the measles and control rubella as these diseases lead to considerable morbidity and mortality especially among under-five children and are important public health problems. This study was aimed to estimate the seroprevalence of measles, mumps and rubella (MMR) antibodies among children of age 5-10 yr in Chandigarh, north India, to provide evidence on prevalent immunity levels. Methods: : This cross-sectional study was conducted in Chandigarh, among 196 randomly selected healthy children (5-10 yr), who received either one or two doses of measles or MMR combination vaccine. Socio-economic background and immunization history were recorded. Blood sample (2 ml) was collected to estimate the MMR IgG antibody titres by using ELISA kits. Results: : Protective seroprevalence of MMR antibodies was 40.8, 75.5 and 86.2 per cent, respectively. The geometric mean titres of MMR IgG antibodies in the study children were 11.3, 50.6 and 54.3 international units (IU)/ ml, respectively. The proportion of seroprotected children for measles was significantly higher among those who had received two or more doses (46.4%) of measles vaccine compared to those who had received single dose (35.6%) (P <0.001). About 16 per cent of children had received single dose of MMR vaccine. Among these, 71.4 and 100 per cent were seroprotected against mumps and rubella, respectively. Interpretation & conclusions: : A large proportion of children aged 5-10 yr lacked protective immunity against measles (60%); about one-fourth (15-25%) were susceptible to infection with mumps and rubella virus. Mumps vaccination may be considered to be included in National Immunization Schedule for children with periodic serosurveillance.

Redox modulatory protective effects of ω-3 fatty acids rich fish oil against experimental colitis.

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.

Oral Delivery of Methylthioadenosine to the Brain Employing Solid Lipid Nanoparticles: Pharmacokinetic, Behavioral, and Histopathological Evidences.

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.

Conflict in the Mechanism and Kinetics of the Barrierless Reaction between SH and NO2 Radicals.

There are some unsettled issues regarding the mechanism and kinetics of an important atmospheric reaction of NO2 radical with the SH radical. The existing mechanism is based on the formation of HSO and NO radicals, both of which can result only along one barrierless channel. However, the detection of NO radical has never been reported though the formation of HSO radical has been followed in some studies to determine the rate constants. The latter are mainly obtained by monitoring the SH decay, but rate constants are reported to be highly conflicting among the existing studies reporting its value ranging from 10-10 to 10-12 cm3 molecule-1 sec-1. The present work attempts to resolve these issues by exploring various reaction pathways through the global reaction route mapping of the potential energy surface at the level of spin-unrestricted and spin-restricted coupled-cluster and density functional theories. The initial association of two radicals was found to proceed via two barrierless modes: (1) S-N association leading to HSNO2 and, (2) S-O association resulting in HSONO, in particular the cis-isomer. The kinetics of the barrierless pathways was investigated through rate constants computed using canonical variational transition state theory (CVTST) along with their temperature and pressure dependence investigated using the master equation. The rate constants calculated using spin-unrestricted methods are found to be in agreement with experimentally observed range of rate constant, and the formation of cis-HSONO (via mode 2) is observed to be the main contributing channel. Contrary to the results of spin-restricted calculations, the barrierless channel (mode 1) leading to the formation of HSNO2 is predicted to involve two bottlenecks when results using spin-unrestricted calculations were analyzed. Notably, the spin-unrestricted calculations predict a prereaction complex for the formation of S-N bond (via mode 1) which has been treated using Miller's unified transition state theory with a two transition state model. The fate of all the species involved in the reaction is critically evaluated in the present work, and the predictions made can be a subject of further experimental and theoretical studies involving radical-radical reactions.

Chemical pathways for poly-anionic isomerisation in the metastable anions of tetra-deprotonated naphthalene: an intra-molecular inter-ring proton-transfer.

A surprising chemical pathway involving an intra-molecular proton-transfer between the two different aromatic rings of naphthalene is revealed while exploring the isomerisation in the metastable tetra-anionic species of tetra-deprotonated naphthalene. The pathways are explored through quantum-mechanical computations employing a global reaction route mapping (GRRM) strategy. Notably, several other pathways traced exhibit interesting aspects of poly-anionic isomerisation in the multiply-charged metastable molecular anions, which can provide valuable insights into the mechanisms of ring closure and expansion leading to species like azulenes, cyclodecapentaene, and phenylvinylacetylene. The metastable poly-anionic species along the pathways were also analysed using a nuclear charge stabilisation procedure while employing conventional density functional theory (DFT) with the B3LYP exchange-correlation functional as well as long-range and dispersion corrected DFT/ωB97XD and DFT-D3 methods. Interestingly, the charge stabilisation method using the DFT/B3LYP was found to be more reliable than the dispersion corrected methods.

Mechanisms for the inversion of chirality: global reaction route mapping of stereochemical pathways in a probable chiral extraterrestrial molecule, 2-aminopropionitrile.

2-Aminopropionitrile (APN), a probable candidate as a chiral astrophysical molecule, is a precursor to amino-acid alanine. Stereochemical pathways in 2-APN are explored using Global Reaction Route Mapping (GRRM) method employing high-level quantum-mechanical computations. Besides predicting the conventional mechanism for chiral inversion that proceeds through an achiral intermediate, a counterintuitive flipping mechanism is revealed for 2-APN through chiral intermediates explored using the GRRM. The feasibility of the proposed stereochemical pathways, in terms of the Gibbs free-energy change, is analyzed at the temperature conditions akin to the interstellar medium. Notably, the stereoinversion in 2-APN is observed to be more feasible than the dissociation of 2-APN and intermediates involved along the stereochemical pathways, and the flipping barrier is observed to be as low as 3.68 kJ/mol along one of the pathways. The pathways proposed for the inversion of chirality in 2-APN may provide significant insight into the extraterrestrial origin of life.

The chickpea root rot complex in Saskatchewan, Canada- detection of emerging pathogens and their relative pathogenicity.

Chickpea fields in Saskatchewan, one of the three Canadian prairie provinces, have suffered from major health issues since 2019, but no definitive cause has been determined. Field surveys were conducted in Saskatchewan in 2020 and 2021 in order to develop a better understanding of root rot pathogens associated with chickpea. Root samples were analyzed for the presence of 11 potential chickpea root rot pathogens using end-point PCR. Fusarium redolens, F. solani and F. avenaceum were the most prevalent pathogen species detected in both survey years. The cause of Fusarium wilt in chickpea, F. oxysporum f. sp. ciceris, was not detected in either year, nor were Phytophthora spp. and Verticillium albo-atrum. Berkeleyomyces sp. was detected in one field in each year, and Verticillium dahliae was detected in several fields sampled in 2021. These two pathogens have not been reported previously on chickpea in Saskatchewan. The prevalence of Fusarium species obtained from 2021 root isolations was similar to that determined by molecular tests, with frequent isolation of F. redolens, F. oxysporum, F. avenaceum and F. solani. A series of indoor pathogenicity testing compared root disease severity caused by a selection of 16 isolates of six Fusarium species and single isolates of V. dahliae, Berkeleyomyces sp. and Macrophomina phaseolina. Results showed that select isolates of F. avenaceum were the most aggressive of the Fusarium isolates on chickpea. Despite relatively low inoculum density, a highly aggressive isolate of F. avenaceum caused severe stunting and more root rot symptoms than single isolates of V. dahliae, Berkeleyomyces sp. and M. phaseolina under the test conditions.

Bacterial metabolite butyrate in modulating sorafenib-targeted microRNAs to curtail its resistance in hepatocellular carcinoma.

BACKGROUND AND AIM: The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC. METHODS: Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays. RESULTS: In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells. CONCLUSION: This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma.

Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs. 1,2,3-Triazole is a miraculous nucleus in medicinal chemistry and the first choice for development of multifunctional hybrid molecules. Apart from that, it is an integral component of various drugs in clinical trials as well as in clinical practice. This review is focused on the pathogenesis of Alzheimer's disease and 1,2,3-triazole containing derivatives developed in recent decades as potential anti-Alzheimer's agents. The review will provide (A) precise insight of various established targets of Alzheimer's disease including cholinergic, amyloid, tau, monoamine oxidases, glutamate, calcium, and reactive oxygen species hypothesis and (B) design hypothesis, structure-activity relationships, and pharmacological outcomes of 1,2,3-triazole containing multifunctional anti-Alzheimer's agents. This review will provide a baseline for various research groups working on Alzheimer's drug development in designing potent, safer, and effective multifunctional anti-Alzheimer's candidates of the future.

The Current Landscape of Bioactive Molecules against DENV: A Systematic Review.

With a 30-fold increase in incidence over the previous 50 years, dengue fever is now the most widespread viral disease transmitted by mosquitoes in the world. The intricate interaction of the human defense system, hereditary predisposition, and specific bitterness elements is more likely to be the pathogenesis of dengue. There are presently no viable treatments for dengue. Synthetic drugs which are used against this ailment also show major side effects. There must be a deeper understanding of the underlying mechanism generating severe symptoms to develop auguring markers, cutting-edge diagnostics, and treatments and finally a well-rounded and secure antiserum. Hence, the aim is to search for safer and more potent drugs derived from plants. Plants or herbs are mainly targeting replication or its enzyme or specific stereotypes, though an exact mechanism of phytoconstituents interfering with the viral replication is still undiscovered. The present attempt provided the update with the objective to bringing up forward pathophysiological eventualities involved in dengue virus along with the naturally derived treatment relevant to provide the impregnable therapy by evading the noxious symptoms for dengue fever. Governor's plum, Cryptocarya chartacea, magnolia berry, and Chinese ginger are such plants exhibiting many effective phytoconstituents against DENV and can be further explored for novel drug discovery by medicinal scientists.

The hidden players: Shedding light on the significance of post-translational modifications and miRNAs in Alzheimer's disease development.

Alzheimer's disease (AD) is the most prevalent, expensive, lethal, and burdening neurodegenerative disease of this century. The initial stages of this disease are characterized by a reduced ability to encode and store new memories. Subsequent cognitive and behavioral deterioration occurs during the later stages. Abnormal cleavage of amyloid precursor protein (APP) resulting in amyloid-beta (Aß) accumulation along with hyperphosphorylation of tau protein are the two characteristic hallmarks of AD. Recently, several post-translational modifications (PTMs) have been identified on both Aß as well as tau proteins. However, a complete understanding of how different PTMs influence the structure and function of proteins in both healthy and diseased conditions is still lacking. It has been speculated that these PTMs might play vital roles in the progression of AD. In addition, several short non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. The miRNAs are single-stranded RNAs that control gene expression by causing mRNA degradation, deadenylation, or translational repression and have been implicated in the regulation of several neuronal and glial activities. The lack of comprehensive understanding regarding disease mechanisms, biomarkers, and therapeutic targets greatly hampers the development of effective strategies for early diagnosis and the identification of viable therapeutic targets. Moreover, existing treatment options for managing the disease have proven to be ineffective and provide only temporary relief. Therefore, understanding the role of miRNAs and PTMs in AD can provide valuable insights into disease mechanisms, aid in the identification of biomarkers, facilitate the discovery of novel therapeutic targets, and inspire innovative treatments for this challenging condition.

Sunflower protein isolates-composition, extraction and functional properties.

The demand of proteins from both plant and animal origin is growing throughout the world. But the proteins obtained from animals have an environmental effect and are expensive in market. Sunflower seeds are particularly intriguing among plant proteins since they are widely available have high protein content, nutritive value and functionalities. The quantity of anti-nutritional components in sunflower has been shown very low as compared to other plant sources. The governing factor which decides the applicability of sunflower proteins is its functional properties despite the absence of anti-nutritional compounds. The emulsification properties are comparable to soy protein isolates which increases the use of sunflower protein. However, foaming and gelling properties are not promising. But these properties can be improved by modification of proteins and eventually can be used for specific applications.

miR-23b-3p Modulating Cytoprotective Autophagy and Glutamine Addiction in Sorafenib Resistant HepG2, a Hepatocellular Carcinoma Cell Line.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy with increasing cancer deaths worldwide. HCC is mainly diagnosed at its advanced stage, and treatment with FDA-approved sorafenib, the multikinase inhibitor drug, is advised. Acquired resistance against sorafenib develops through several pathways involving hypoxia, autophagy, high glycolysis, or glutaminolysis. Small non-coding RNAs, similar to microRNAs (miRNAs), are also known to affect sorafenib resistance in HCC. However, there is a lack of information regarding the significance of differentially expressed miRNA (if any) on autophagy and glutamine regulation in sorafenib-resistant HCC. METHODS: The expression of autophagy and glutaminolysis genes was checked in both parental and sorafenib resistant HepG2 cell lines by real-time PCR. MTT and Annexin/PI assays were also performed in the presence of inhibitors such as chloroquine (autophagy inhibitor) and BPTES (glutaminolysis inhibitor). Next generation sequencing and in silico analysis were performed to select autophagy and glutamine addiction-specific microRNA. Selected miRNA were transfected into both HepG2 cells to examine its effect on autophagy and glutamine addiction in regulating sorafenib-resistant HCC. RESULTS: Our in vitro study depicted a higher expression of genes encoding autophagy and glutaminolysis in sorafenib-resistant HepG2 cells. Moreover, inhibitors for autophagy (chloroquine) and glutaminolysis (BPTES) showed a diminished level of cell viability and augmentation in cell apoptosis of sorafenib-resistant HepG2 cells. NGS and real-time PCR demonstrated the downregulated expression of miR-23b-3p in sorafenib-resistant cells compared to parental cells. In silico analysis showed that miR-23b-3p specifically targeted autophagy through ATG12 and glutaminolysis through GLS1. In transfection assays, mimics of miR-23b-3p demonstrated reduced gene expression for both ATG12 and GLS1, decreased cell viability, and increased cell apoptosis of sorafenib-resistant HepG2 cells, whereas the antimiRs of miR-23b-3p demonstrated contrasting results. CONCLUSION: Our study highlights the cytoprotective role of autophagy and glutamine addiction modulated by miR-23b-3p (tumor suppressor), suggesting new approaches to curb sorafenib resistance in HCC.

Enhanced photo-degradation of N-methyl-2-pyrrolidone (NMP): Influence of matrix components, kinetic study and artificial neural network modelling.

This study investigates the degradation of N-methyl-2-pyrrolidone (NMP) by UV-C and UV-C/PMS-treatment processes. The degradation of NMP was less than 2% by UV-C photolysis. To enhance the degradation, PMS was used as a source of sulphate (SO4• -) and hydroxyl (HO•) radicals in the UV-C photolysis treatment system. The operational parameters such as initial pH and concentration of NMP and PMS and water matrix elements were studied to understand their effects on degradation. At pH = 6.3, λ = 260 nm, initial concentration of NMP = 10 mg/L, PMS = 300 mg/L and carbonate ion = 150 mg/L, the degradation of NMP was found to be 97.5%, along with 26.86% of TOC removal. The bicarbonate ions, nitrate ions, and chloride ions showed the inhibitory effect on the degradation of NMP. The NMP degradation was governed by pseudo first order kinetics. SO4• - was found to be the dominating degradation species through the radical quenching studies. The intermediates formed during the degradation were identified through LC-MS analysis, and a degradation pathway was proposed. The experimental data was successfully validated through the application of the developed ANN model. The R2 between expected and experimental outcomes was 0.97. The developed ANN model was successful in predicting the degradation of NMP in the given reaction conditions with the prediction accuracy of 90.91% and RMSE of 3.54.

Therapeutic Modalities in Head-Neck Neoplasia and Prognostication: A Review.

Neoplasia of the head and the neck necessitates intervention, surgical or otherwise, as the site and stage of the pathology may dictate. The various therapeutic modalities employed and prognosis has been reviewed.

Efficacy of Brentuximab Vedotin and Nivolumab in Refractory or Relapsed Hodgkin Lymphoma: A Systematic Review.

The central dilemma in treating patients with refractory or relapsed classical Hodgkin lymphoma (RRHL) is the developed resistance to chemotherapy. In recent years, significant advances have been made with the introduction of targeted immunotherapy such as brentuximab vedotin (BV) and nivolumab (NV). As monotherapy, BV and NV have demonstrated high response rates but with an opportunity for disease progression. In other studies, BV or NV is given in combination with chemotherapy as a bridge to hematopoietic stem cell transplantation for curative therapy. This review will investigate the effect of BV and NV as single agents, in combination with each other, or given concurrently with chemotherapy on the response and survival rate of patients with RRHL.

Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy.

Metastasis-initiating cells (MICs) display stem cell-like features, cause metastatic recurrences and defy chemotherapy, which leads to patients' demise. Here we show that prostate and breast cancer patients harbor contingents of tumor cells with high expression of CX3CR1, OCT4a (POU5F1), and NANOG. Impairing CX3CR1 expression or signaling hampered the formation of tumor spheroids by cell lines from which we isolated small subsets co-expressing CX3CR1 and stemness-related markers, similarly to patients' tumors. These rare CX3CR1High cells show transcriptomic profiles enriched in pathways that regulate pluripotency and endowed with metastasis-initiating behavior in murine models. Cancer cells lacking these features (CX3CR1Low) were capable of re-acquiring CX3CR1-associated features over time, implying that MICs can continuously emerge from non-stem cancer cells. CX3CR1 expression also conferred resistance to docetaxel, and prolonged treatment with docetaxel selected CX3CR1High phenotypes with de-enriched transcriptomic profiles for apoptotic pathways. These findings nominate CX3CR1 as a novel marker of stem-like tumor cells and provide conceptual ground for future development of approaches targeting CX3CR1 signaling and (re)expression as therapeutic means to prevent or contain metastasis initiation.