Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Targeting the Key Signaling Pathways in Breast Cancer: From Molecular Mechanism to Therapeutic Interventions.

Breast cancer is a public health issue in developing and developed countries. Nowadays, the concept of BCSC (breast cancer stem cell) is gaining popularity among oncology researchers. The breast cancer stem cell is a tiny cell fraction inside the tumor mass that shows features that look like stem cells that are implicated in the genesis, recurrence, and metastasis of breast cancer tumors. Extracellular cues, mutations, and epigenetic control all contribute to the intricacy of gene expression control in Breast cancer stem cells. Thus, signaling pathways identified in breast cancer are Hedgehog and NOTCH, signal transducer and transcription 3, wingless-type MMTV integration site family (Wnt)/-catenin, and nuclear factor-kappa B, particularly connected with a phenotype of stem cell. Furthermore, the tumor microenvironment, such as hypoxic regions, can impact these BCSCs. Various approved signaling pathway targeted molecules have been patented, which show protective effects against breast cancer and have been used in clinical uses. PARP inhibitors are found to be very useful in the treatment of breast cancer. Promoting studies on the molecular pathways underlying the development of cancer in breast cancer patients was one of the main objectives of this study topic. The objective of this review Topic was to discover new intrinsic and extrinsic molecular pathways. Research focusing on novel signaling pathways that may lead to novel treatments or identifying patients at-risk of not responding to standard therapy approaches were the areas of focus we highlighted. The paper covers the linkage between breast cancer stem cells and cellular signaling, the tumor microenvironment in BC, and the relevance of signaling pathways and their therapeutic interventions. The review also covered patent applications associated with these signaling pathways and their prospects.

Biological Evaluation and Binding Mechanism of 5-HT7 Specific Arylpiperazinyl-Alkyl Benzothiazolone: Radiobiology and Photo-physical Studies.

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.

CstMYB1R1, a REVEILLE-8-like transcription factor, regulates diurnal clock-specific anthocyanin biosynthesis and response to abiotic stress in Crocus sativus L.

KEY MESSAGE: CstMYB1R1 acts as a positive regulator of Crocus anthocyanin biosynthesis and abiotic stress tolerance which was experimentally demonstrated through molecular analysis and over-expression studies in Crocus and Nicotiana. Regulatory mechanics of flavonoid/anthocyanin biosynthesis in Crocus floral tissues along the diurnal clock has not been studied to date. MYB proteins represent the most dominant, functionally diverse and versatile type of plant transcription factors which regulate key metabolic and physiological processes in planta. Transcriptome analysis revealed that MYB family is the most dominant transcription factor family in C. sativus. Considering this, a MYB-related REVEILLE-8 type transcription factor, CstMYB1R1, was explored for its possible role in regulating Crocus flavonoid and anthocyanin biosynthetic pathway. CstMYB1R1 was highly expressed in Crocus floral tissues, particularly tepals and its expression was shown to peak at dawn and dusk time points. Anthocyanin accumulation also peaked at dawn and dusk and was minimum at night. Moreover, the diurnal expression pattern of CstMYB1R1 was shown to highly correlate with Crocus ANS/LDOX gene expression among the late anthocyanin pathway genes. CstMYB1R1 was shown to be nuclear localized and transcriptionally active. CstMYB1R1 over-expression in Crocus tepals enhanced anthocyanin levels and upregulated transcripts of Crocus flavonoid and anthocyanin biosynthetic pathway genes. Yeast one hybrid (Y1H) and GUS reporter assay confirmed that CstMYB1R1 interacts with the promoter of Crocus LDOX gene to directly regulate its transcription. In addition, the expression of CstMYB1R1 in Nicotiana plants significantly enhanced flavonoid and anthocyanin levels and improved their abiotic stress tolerance. The present study, thus, confirmed positive role of CstMYB1R1 in regulating Crocus anthocyanin biosynthetic pathway in a diurnal clock-specific fashion together with its involvement in the regulation of abiotic stress response.

CstPIF4 Integrates Temperature and Circadian Signals and Interacts with CstMYB16 to Repress Anthocyanins in Crocus.

Crocus sativus has emerged as an important crop because it is the only commercial source of saffron that contains unique apocarotenoids. Saffron is composed of dried stigmas of Crocus flower and constitutes the most priced spice of the world. Crocus floral organs are dominated by different classes of metabolites. While stigmas are characterized by the presence of apocarotenoids, tepals are rich in flavonoids and anthocyanins. Therefore, an intricate regulatory network might play a role in allowing different compounds to dominate in different organs. Work so far done on Crocus is focussed on apocarotenoid metabolism and its regulation. There are no reports describing the regulation of flavonoids and anthocyanins in Crocus tepals. In this context, we identified an R2R3 transcription factor, CstMYB16, which resembles subgroup 4 (SG4) repressors of Arabidopsis. CstMYB16 is nuclear localized and acts as a repressor. Overexpression of CstMYB16 in Crocus downregulated anthocyanin biosynthesis. The C2/EAR motif was responsible for the repressor activity of CstMYB16. CstMYB16 binds to the promoter of the anthocyanin biosynthetic pathway gene (LDOX) and reduces its expression. CstMYB16 also physically interacts with CstPIF4, which in turn is regulated by temperature and circadian clock. Thus, CstPIF4 integrates these signals and forms a repressor complex with CstMYB16, which is involved in the negative regulation of anthocyanin biosynthesis in Crocus. Independent of CstPIF4, CstMYB16 also represses CstPAP1 expression, which is a component of the MYB-bHLH-WD40 (MBW) complex and positively controls anthocyanin biosynthesis. This is the first report on identifying and describing regulators of anthocyanin biosynthesis in Crocus.

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats.

AIM: To investigate the aldose reductase (AR) inhibition capacity of astragalin (AST) against streptozoticin-induced diabetic cataracts (DCs) in rats. METHODS: Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor (AAH) of pH 7.8 at room temperature with cataract-causing substance (55 mmol/L of galactose) and in vivo studies were performed on rats via induction with streptozotocin. AST was administered at different dose levels and scrutinize for DC activity. RESULTS: In diabetic rats, AST improved the body weight, blood insulin, and glucose as well as the levels of galactitol in a dose-dependent way, other biochemical parameters i.e. inflammatory mediators and cytokines, and also suppress AR activity. The level of the antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity were also altered on a diabetic lens after the administration of the AST. CONCLUSION: AST protects against lens opacification to avoid cataracts and polyols formation, indicating that it could be used as a potential therapeutic agent for diabetes.

Characteristics of patients who use yoga for pain management in Indian yoga and naturopathy settings: a retrospective review of electronic medical records.

Objectives: The aim of this study is to identify the characteristics of patients who underwent yoga therapy for pain in yoga and naturopathy clinical settings in India. Methods: Electronic medical records of patients who received yoga therapy for pain in three inpatient yoga and naturopathy hospitals were reviewed retrospectively from January 2021 to September 2022. Demographic characteristics and details on pain condition, socioeconomic status, comorbidities, ancillary therapies received, and insurance status were collected. In addition, we prospectively collected data on adherence to yoga practice through a telephonic interview. Results: A total of 984 patients were identified from a pool of 3,164 patients who received yoga therapy for pain for an average of 9.48 (1.13) days. Patients aged between 8 and 80 underwent therapy for varying pain conditions and diseases that include pain in the extremities, pain due to infection, trauma, degenerative diseases, autoimmune diseases, and spine and neurological diseases. The majority of the patients were females (66.3%), from middle class families (74.8%), and who did not have any insurance coverage (93.8%). Most of the patients were under naturopathy treatment (99.8%), followed by ayurveda (56%), and physiotherapy (49.3%), along with yoga therapy. All patients reported a significant reduction in pain post-integrated yoga therapy (p < 0.001). Adherence to yoga was significantly associated with underlying pain conditions, the presence of comorbidities, the types of therapies used, and socioeconomic status (p < 0.001). Conclusion: This study highlights the real-time application of yoga in pain management in Indian yoga and naturopathy settings, as well as implications for future research.

An Insight on Skin Cancer About Different Targets With Update on Clinical Trials and Investigational Drugs.

Cancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth.

Childhood-Onset ANCA- Associated Vasculitis: single center experience from Central California.

BACKGROUND: Childhood-onset ANCA-associated vasculitides (AAV) are characterized by necrotizing inflammation and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pediatric data is scare and there have been no prior studies examining the characteristics of pediatric AAV in Central California. METHODS: This retrospective study comprised AAV patients ≤18 years of age, diagnosed between 2010 and 2021, in Central California. We analyzed initial presentation including demographics, clinical, laboratory characteristics, treatment, and initial outcomes. RESULTS: Of 21 patients with AAV, 12 were categorized as MPA and 9 with GPA. Median age at diagnosis was 13.7 years in MPA cohort and 14 years in GPA. MPA cohort were majority females (92% versus 44%). 57% of the cohort were racial/ethnic minority including Hispanics (n = 9), Asians (n = 2), multiracial (n = 1) and 43% were white (n = 9). MPA patients were more frequently Hispanic (67%), meanwhile GPA patients were frequently white (78%). Median duration of symptoms prior to diagnosis was 14 days in MPA cohort and 21 days in GPA cohort. Renal involvement was frequent (100% in MPA and 78% in GPA). GPA cohort had frequent ear, nose and throat (ENT) involvement (89%). All patients were ANCA positive. All Hispanic patients were MPO positive, meanwhile 89% of white patients were PR3 positive. MPA cohort tended towards more severe disease with 67% requiring ICU admission and 50% requiring dialysis. Two deaths were reported in MPA cohort, related to Aspergillus pneumonia and pulmonary hemorrhage. In MPA cohort, 42% received cyclophosphamide in combination with steroids and 42% received rituximab in combination with steroids. GPA patients received cyclophosphamide, either with steroids alone (78%) or in combination with steroids and rituximab (22%). CONCLUSIONS: Microscopic polyangiitis was the most frequent AAV subtype with female preponderance, shorter duration of symptoms at onset and higher proportion of racial/ ethnic minority patients. Hispanic children demonstrated frequent MPO positivity. Trends towards higher rates of ICU requirement and need for dialysis upon initial presentation was noted in MPA. Patients with MPA received rituximab more frequently. Future prospective studies are needed to understand differences in presentation and outcomes in childhood onset AAV between diverse racial-ethnic groups.

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.

Correction: Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation.

[This corrects the article DOI: 10.1039/C8RA03500H.].

The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.

Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i's) in combination with chemotherapy have shown promising results in preclinical studies but minimal efficacy with substantial toxicity in clinical trials. To explore novel combinational strategies that can overcome these limitations, we performed an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identified thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a novel determinant of CHK1i sensitivity. We established a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR1 inhibitor auronafin, an anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, these findings identify a new pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

The rose INFLORESCENCE DEFICIENT IN ABSCISSION-LIKE genes, RbIDL1 and RbIDL4, regulate abscission in an ethylene-responsive manner.

KEY MESSAGE: RbIDL1 and RbIDL4 are up-regulated in an ethylene-responsive manner during rose petal abscission and restored the Arabidopsis ida-2 mutant abscission defect suggesting functional conservation of the IDA pathway in rose. Abscission is an ethylene-regulated developmental process wherein plants shed unwanted organs in a controlled manner. The INFLORESCENCE DEFICIENT IN ABSCISSION family has been identified as a key regulator of abscission in Arabidopsis, encoding peptides that interact with receptor-like kinases to activate abscission. Loss of function ida mutants show abscission deficiency in Arabidopsis. Functional conservation of the IDA pathway in other plant abscission processes is a matter of interest given the discovery of these genes in several plants. We have identified four members of the INFLORESCENCE DEFICIENT IN ABSCISSION-LIKE family from the ethylene-sensitive, early-abscising fragrant rose, Rosa bourboniana. All four are conserved in sequence and possess well-defined PIP, mIDa and EPIP motifs. Three of these, RbIDL1, RbIDL2 and RbIDL4 show a three-fourfold increase in transcript levels in petal abscission zones (AZ) during ethylene-induced petal abscission as well as natural abscission. The genes are also expressed in other floral tissues but respond differently to ethylene in these tissues. RbIDL1 and RbIDL4, the more prominently expressed IDL genes in rose, can complement the abscission defect of the Arabidopsis ida-2 mutant; while, promoters of both genes can drive AZ-specific expression in an ethylene-responsive manner even in Arabidopsis silique AZs indicating recognition of AZ-specific and ethylene-responsive cis elements in their promoters by the abscission machinery of rose as well as Arabidopsis.

Effect of health education-based yoga & naturopathy lifestyle interventions on personality of patients with non-communicable diseases: A randomized controlled trial.

BACKGROUND: Personality traits play a role in the progression and management of chronic diseases. However, a change in personality is seldom considered an outcome in the management of chronic diseases. The present study explored if a health education-based yoga & naturopathy lifestyle intervention group (HYNLG) can induce change in the personality traits, vitality, quality of life (QoL), and satisfaction in patients with non-communicable diseases compared to a therapy-centric yoga & naturopathy lifestyle intervention (TYNLG). METHODS: This randomized control trial included 56 participants who were equally randomized into the HYNLG and TYNLG groups. Both groups received a 10-day inpatient regimen that included hydrotherapy, mud therapy, diet therapy, supervised fasting, sunbathing, acupressure, and massage therapy. Additionally, HYNLG received a 10-day orientation (1 h/d) on concepts centered around belief systems, lifestyle changes, and their impact on health. Vedic Personality Inventory, SF-12 QoL questionnaire, visual analog scale, Hamilton Anxiety Inventory, and Visit-Specific Patient Satisfaction Questionnaire were used as outcome measures. The changes between the time points were analyzed using parametric and non-parametric tests, and Pearson correlation was used to investigate the association between the variables. RESULTS: The Sattva (balance and stability) personality trait has significantly increased in HYNLG, while the Rajas (activity and imbalance) and Tamas (inertia and dullness) personalities have decreased. HYNLG also demonstrated a significant improvement in mental QoL, vitality, anxiety reduction, and patient satisfaction when compared to TYNLG. CONCLUSION: These findings may have serious clinical and public health implications as they provide insights on the usefulness of introducing a health education component into lifestyle modification programs.

Acidic graphene organocatalyst for the superior transformation of wastes into high-added-value chemicals.

Our dependence on finite fossil fuels and the insecure energy supply chains have stimulated intensive research for sustainable technologies. Upcycling glycerol, produced from biomass fermentation and as a biodiesel formation byproduct, can substantially contribute in circular carbon economy. Here, we report glycerol's solvent-free and room-temperature conversion to high-added-value chemicals via a reusable graphene catalyst (G-ASA), functionalized with a natural amino acid (taurine). Theoretical studies unveil that the superior performance of the catalyst (surpassing even homogeneous, industrial catalysts) is associated with the dual role of the covalently linked taurine, boosting the catalyst's acidity and affinity for the reactants. Unlike previous catalysts, G-ASA exhibits excellent activity (7508 mmol g-1 h-1) and selectivity (99.9%) for glycerol conversion to solketal, an additive for improving fuels' quality and a precursor of commodity and fine chemicals. Notably, the catalyst is also particularly active in converting oils to biodiesel, demonstrating its general applicability.

Hormones regulate the flowering process in saffron differently depending on the developmental stage.

Flowering in saffron is a highly complex process regulated by the synchronized action of environmental cues and endogenous signals. Hormonal regulation of flowering is a very important process controlling flowering in several plants, but it has not been studied in saffron. Flowering in saffron is a continual process completed in months with distinct developmental phases, mainly divided into flowering induction and flower organogenesis/formation. In the present study, we investigated how phytohormones affect the flowering process at different developmental stages. The results suggest that different hormones differentially affect flower induction and formation in saffron. The exogenous treatment of flowering competent corms with abscisic acid (ABA) suppressed both floral induction and flower formation, whereas some other hormones, like auxins (indole acetic acid, IAA) and gibberellic acid (GA), behaved contrarily at different developmental stages. IAA promoted flower induction, while GA suppressed it; however, GA promoted flower formation, whereas IAA suppressed it. Cytokinin (kinetin) treatment suggested its positive involvement in flower induction and flower formation. The expression analysis of floral integrator and homeotic genes suggests that ABA might suppress floral induction by suppressing the expression of the floral promoter (LFY, FT3) and promoting the expression of the floral repressor (SVP) gene. Additionally, ABA treatment also suppressed the expression of the floral homeotic genes responsible for flower formation. GA reduces the expression of flowering induction gene LFY, while IAA treatment upregulated its expression. In addition to these genes, a flowering repressor gene, TFL1-2, was also found to be downregulated in IAA treatment. Cytokinin promotes flowering induction by increasing the expression levels of the LFY gene and decreasing the TFL1-2 gene expression. Moreover, it improved flower organogenesis by increasing the expression of floral homeotic genes. Overall, the results suggest that hormones differently regulate flowering in saffron via regulating floral integrator and homeotic gene expression.

Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer.

BACKGROUND: The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable. OBJECTIVE: This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells. METHODS: Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1ß production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. RESULTS: Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1ß production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels. CONCLUSIONS: We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.

Evaluation of advanced, pathophysiologic new targets for imaging of CNS.

The inadequate information about the in vivo pathological, physiological, and neurological impairments, as well as the absence of in vivo tools for assessing brain penetrance and the efficiency of newly designed drugs, has hampered the development of new techniques for the treatment for variety of new central nervous system (CNS) diseases. The searching sites such as Science Direct and PubMed were used to find out the numerous distinct tracers across 16 CNS targets including tau, synaptic vesicle glycoprotein, the adenosine 2A receptor, the phosphodiesterase enzyme PDE10A, and the purinoceptor, among others. Among the most encouraging are [18 F]FIMX for mGluR imaging, [11 C]Martinostat for Histone deacetylase, [18 F]MNI-444 for adenosine 2A imaging, [11 C]ER176 for translocator protein, and [18 F]MK-6240 for tau imaging. We also reviewed the findings for each tracer's features and potential for application in CNS pathophysiology and therapeutic evaluation investigations, including target specificity, binding efficacy, and pharmacokinetic factors. This review aims to present a current evaluation of modern positron emission tomography tracers for CNS targets, with a focus on recent advances for targets that have newly emerged for imaging in humans.

Expression of concern: Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation.

Expression of concern for 'Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation' by Ekta Yadav et al., RSC Adv., 2018, 8, 21621-21635, https://doi.org/10.1039/C8RA03500H.

Clinical Significance of Overexpression of Oct4 in Advanced Stage Gallbladder Carcinoma.

BACKGROUND: Oct4 has critical role in maintaining pluripotency, proliferative potential, and self-renewal capacity in embryonic stem and germ cells. Although Oct4 has been shown to be upregulated in many cancers, its clinical significance in gallbladder carcinoma is poorly understood. METHODS: We studied the expression profile of Oct4 in 61 GBC and 30 chronic cholecystitis (as control) using real time RT-PCR, western blotting, and immunohistochemistry. The expression data was correlated with clinico-pathological parameters. The diagnostic utility was assessed through ROC curve, and prognostic value was analyzed by Kaplan-Meier method. RESULTS: Oct4 was significantly upregulated at mRNA as well as protein levels. The higher mRNA expression shows significant association with late stage, late T stage, and higher grade of tumor. A significant positive correlation was also observed with stage, T stage, and tumor grade. Sum score analysis of protein expression shows positive correlation with stage and the presence or absence of gallstone in tumor samples. The ROC curve analysis revealed the moderate diagnostic potential of Oct4. Kaplan-Meier analysis showed that patients having higher expression of Oct4 were having low mean survival compared with the patients with lower Oct4 expression. CONCLUSION: In conclusion, our data suggests that higher expression of Oct4 may serve as potential biological indicator for tumor aggressiveness and poor prognosis of GBC.