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Due to the heterogeneous nature of depression, the underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers to serve as precise targets for therapeutic efficacy. The extensive research efforts over the past decades have not yielded much success, and the currently used first-line conventional antidepressants are still ineffective for close to 66% of patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial to only a fraction of patients, with some eventually developing treatment resistance. Here, we review evidence from both preclinical and clinical studies on the pathogenesis of depression and antidepressant treatment response. We also discuss the efficacy of the currently used pharmacological and non-pharmacological approaches, as well as the novel emerging therapies. The review reveals that the underlying mechanisms in the pathogenesis of depression and antidepressant response, are not specific, but rather involve an interplay between various neurotransmitter systems, inflammatory mediators, stress, HPA axis dysregulation, genetics, and other psycho-neurophysiological factors. None of the current depression hypotheses sufficiently accounts for the interactional mechanisms involved in both its etiology and treatment response, which could partly explain the limited success in discovering efficacious antidepressant treatment. Effective management of treatment-resistant depression (TRD) requires targeting several interactional mechanisms, using subtype-specific and/or personalized therapeutic modalities, which could, for example, include multi-target pharmacotherapies in augmentation with psychotherapy and/or other non-pharmacological approaches. Future research guided by interaction mechanisms hypotheses could provide more insights into potential etiologies of TRD, precision biomarker targets, and efficacious therapeutic modalities. [ABSTRACT FROM AUTHOR]

Catechin is one of the prestigious phytoconstituent obtained from the divine wealth of nature. It is a polyphenolic constituent which is broadly distributed in plant kingdom and tea, legumes and rubeaceous plants are rich sources of it. Various research groups have extracted and isolated it by using different analytical techniques due to its diverse pharmacological profile. It is evident in nature that catechin possesses promising anti-inflammatory, neuroprotective, antioxidant, antibacterial, anticancer and anti-viral properties. There are several formulations reported which are intended for multiple uses where catechins are important ingredient. This review discusses the various analytical techniques employed for the extraction and isolation of catechins from various sources, as well as a summary of various reported formulations. The authors also discuss the various pharmacological activities exhibited by catechins, along with the significant outcomes and plausible mode of action. In addition, the review provides an insight into various synthetic and biosynthetic procedures for catechins, along with a description of various clinical trials and patents. In the lateral sections of this compilation, an insight to various synthetic/biosynthetic procedures for catechins has been provided along with description to various clinical trials and patents. Although a lot of progress has been made towards exploration of catechins, still these are associated with some issues of bioavailability and unclear modes of action, which need to be resolved in upcoming times. This review is more comprehensive on catechins, as it covers a wider range of topic includings; analytical techniques for the extraction and isolations of catechins, formulations containing catechins, pharmacological activities, synthetic and biosynthetic procedure, clinical trials as well as patents. The review also provide a more in-depth discussion of the pharmacological activities of catechins, including the significant outcomes and plausible mode of action. The article also highlights the need for the further research to address the issues of bioavailability and unclear modes of action associated with the catechin. This is an important area of research, as it is essential to understand the ADME to develop effective catechin-based therapies. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) continues to be the leading cause of cancer death worldwide, driven by environmental factors like smoking and genetic predispositions. LUAD has a high mortality rate, and new biomarkers are urgently needed to improve treatment strategies and patient management. Programmed cell death (PCD) is involved in tumor progression and response to treatment. Therefore, there is a need for an extensive study of the role and functions of PCD-related genes (PCDRGs) in lung adenocarcinoma so as to understand the pathophysiologic features of lung adenocarcinoma. Methods: Based on TCGA and GEO databases, this research is aimed at screening differentially expressed PCD-related genes in lung adenocarcinoma. We conducted GO, and KEGG analysis to establish the link between these genes and biological processes. By applying various machine learning algorithms such as CoxBoost analysis, we developed PCD-related indices (PCDI) that were used to verify their ability to predict prognosis with the use of other datasets. This was done in addition to exploring the biological functions of PCD genes associated with lung adenocarcinoma by assessing the relationship between immune cell components of tumor microenvironment and PCD genes together with examining how they affect drug sensitivity. Results: The research presented in this article offers significant insights into LUAD. The authors identified 113 PCDRGs that were differentially expressed in LUAD. These genes are implicated in various biological functions, including High risk ing apoptosis, ferroptosis, and pathways specific to non-small cell lung cancer. Notably, the PCDI proved effective in distinguishing between High risk and Low risk LUAD patients, demonstrating a higher accuracy in prognosis prediction compared to traditional clinical indicators such as age and gender. This high prediction accuracy was validated in both test and validation cohorts. Additionally, these genes showed significant correlations with immune cell infiltration and drug sensitivity in LUAD patients. Conclusion: We analysed the expression and function of PCDRGs in LUAD and revealed their correlation with patient survival, the immune microenvironment and drug sensitivity. The constructed PCDI model provides a scientific basis for the personalised treatment of lung adenocarcinoma, and future optimisation of treatment strategies based on these genes may improve patient clinical outcomes. [ABSTRACT FROM AUTHOR]

The bitter gourd (Momordica charantia L.), has been remained a well-known ethnic medicinal vegetable, used traditionally as a pharma food to obtain a plenty of pharmacological benefits. However, which fraction of fruit is most effective for provision of bioactive components, has been remained undiscovered yet. This study examined the chemical composition, phytochemicals and antioxidant activities of peel, flesh, and seeds of bitter gourd. Our results showed that fat (3.50 ± 0.03%) and protein (3.40 ± 0.06%) content were found to be significantly (P < 0.05) high in bitter gourd seed powder (BSP), whereas ash (6.26 ± 0.06%) and fiber (5.46 ± 0.10%) in bitter gourd peel powder (BPP). Microminerals including Fe, Zn, Cu and Mn were found significantly (P < 0.05) high in BSP, with values 3.95 ± 0.05, 4.92 ± 0.04, 2.44 ± 0.04 and 1.32 ± 0.20 mg/100 g, respectively, whereas, macrominerals, Ca (74.90 ± 0.60 mg/100 g) and Mg (52.59 ± 0.20 mg/100 g), in bitter gourd flesh powder (BFP). Total phenolic content (27.78 ± 0.95 mg GAE/100 g), total flavonoid content (12.18 ± 0.08 mg QE/100 g) and total antioxidant activity (16.87 ± 0.11 mg trolox/100 g) was highest in BSP. However, BFP exhibited the greatest total carotenoid content (93.45 ± 0.40 mg/100 g) and β–carotene content (41.72 ± 0.15 mg/100 g). HPLC analysis revealed that all fractions of bitter gourd were loaded with bioactives, as naringenin and catechin were highest in BFP, epicatechin, ferulic acid, kaempferol and p-coumaric acid were highest in BPP, whereas, chlorogenic acid, caffeic acid, gallic acid and apigenin were highest in BSP. As compared to BFP and BPP, BSP exhibited the high concentration of important bioactive components, therefore instead of discarding these waste by-products of bitter gourd could be utilized as source of bioactives.Article highlights: Momordica charantia peel, flesh and seeds were explored for phytochemicals through conversion into powders and ethanolic extracts. Highest minerals, fat, protein, phenolics and flavonoids found in seeds, highest ash and fiber in peel, and highest carotenoids in flesh Naringenin, catechin, epicatechin, ferulic acid, kaempferol, p-coumaric acid and chlorogenic acid were major bioactives in bitter gourd [ABSTRACT FROM AUTHOR]

The genus Tamarix in the Tamaricaceae family consists of more than 100 species of halophyte plants worldwide that are mainly used to improve saline-alkali land and for coastal windbreaks, sand fixation, and afforestation in arid areas. A considerable number of species in this genus are also used as traditional medicines to treat various human diseases, especially in Asian and African countries. This review presents a comprehensive summary of 655 naturally occurring compounds derived from the genus Tamarix, categorized into flavonoids (18.0%), phenols (13.9%), tannins (9.3%), terpenoids (10.5%), essential oils (31.0%), and others (17.3%). The investigation revealed that the crude extracts and phytochemicals of this genus exhibited significant therapeutic potential, including anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, antibacterial, and antifungal activities. Six species of Tamarix have anticancer effects by causing cancer cell death, inducing autophagy, and stopping cell division. Seven species from the same genus have the potential for treating diabetes by inhibiting α-glycosidase activity, suppressing human islet amyloid polypeptide, regulating blood glucose levels, and modulating autophagy or inflammation. The focus on antibacterial and antidiabetic effects is due to the presence of volatile oil and flavonoid components. Extensive research has been conducted on the biological activity of 30 constituents, including 15 flavonoids, 5 phenols, 3 terpenoids, 1 tannin, and 6 others. Therefore, future research should thoroughly study the mechanisms of action of these and similar compounds. This is the most comprehensive review of the phytochemistry and pharmacological properties of Tamarix species, with a critical assessment of the current state of knowledge. [ABSTRACT FROM AUTHOR]

Terminalia chebula, commonly known as black myrobalan, ink tree and Chebulic myrobalan is a deciduous tree belonging to the family Combretaceae. It is native to the tropical region with the highest occurrence in the South East Asian regions. The plant exhibits a wide spectrum of biological activity due to its phytochemicals such as polyphenols, flavonoids, terpenes, anthocyanins and glycosides. The fruit of T. chebula has been used in several traditional medicinal practices such as Ayurveda, Unani and Siddha for the treatment of different diseases and ailments including chronic diarrhoea, gastroenteritis, constipation, asthma, ulcer, haemorrhoids, cold and cough. The plant has been well reported in the current literature to possess anti-oxidant, anti-bacterial, anti-arthritic, anti-cancerous, anti-diabetic, anti-viral, anti-bacterial, hypo-cholesterolemic, anti-plasmodial, antinociceptive, antiulcerogenic and anti-spermatogenic properties. However, comprehensive reviews on the broad spectrum of bioactivity of this plant are limited in literature. Therefore, this review was designed to critically analyse and summarise the current ethno-medicinal and pharmacological evidence on T. chebula. Owing to its bioactivity, T. chebula possesses great potential to include in modern drug discovery. However, further pre-clinical and clinical studies are warranted for its prospective pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Hydrocotyle bonariensis is an edible herb, that is also used for traditional medical purposes. It is high in antioxidants, phenols, and flavonoids. However, there is limited information on the nutritional composition and the mechanisms by which nutritional and functional constituents of H. bonariensis affect human metabolism. With an aim to identify gaps in evidence to support the mainstream use of H. bonariensis for health and as a functional food, this review summarises current knowledge of the taxonomy, habitat characteristics, nutritional value and health-related benefits of H. bonariensis and its extracts. Ethno-medical practices for the plant are supported by pharmacological studies, yet animal model studies, clinical trials and food safety assessments are needed to support the promotion of H. bonariensis and its derivatives as superfoods and for use in the modern pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Being an agarophyte, Gelidium is extensively exploited for its agar-producing capacity. However, the food value and medicinal importance of this red alga are not to be underestimated. The pharmacological properties of Gelidium species have potential for the pharmaceutical, nutraceutical and cosmeceutical industries. This review collects, identifies and analyzes comprehensively the studies that deal with the bioactive properties of Gelidium species in the last decade. The principal bioactive compounds of Gelidium include R-phycoerythrin, R-phycocyanin, alkaloids, terpenoids, tannins, flavonoids, saponins, coumarins, cardiac glycosides, and steroids. Gelidium in the form of extracts or isolated compounds have been reported to show antibacterial, antioxidant, anticancer, anti-inflammatory, anti-obesity, immunomodulatory, neuroprotective, and antidiabetic properties. Most of the evidence has been reported in various in vitro models. Therefore, further experiments using appropriate animal and human subjects are necessary to develop the preclinical findings into clinical use. The main challenge in developing bioactive compounds on a commercial scale is the sustainable supply of Gelidium biomass that requires integrated seaweed aquaculture through employing biotechnological approaches and effective utilization of industrial byproducts. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a distressing condition that should be treated in specialized pain clinics. Pain clinics offer a holistic, evidence-based approach, including pharmacological, complementary, and invasive treatments. This study aimed to provide preliminary information regarding chronic pain treatments and identify reasons for accessing an important hub-spoke pain clinic network. Methods: A retrospective multicenter cross-sectional study was carried out. A total of 1606 patients' records were included. Patients were selected from the 26 pain clinics of a single region in Italy. Univariate and multivariate logistic regression models were used. Results: Multivariate models showed that the use of opioids were considered effective for severe or moderate pain [odds ratio (OR) 0.41; 95% 0.33–0.51], while the use of invasive treatments (OR 2.45; 95% 1.95–3.06) and the use of complementary therapy (OR 1.87; 95% 1.38–2.51) were associated with severe or moderate pain. Overall, age, sex, nonsteroidal anti-inflammatory drugs (NSAID) use, a combination of NSAIDs, complementary therapies, and a combination of opioids and invasive treatments did not seem to be significantly associated with the nature of pain. Multivariate models confirmed that clinical parameters such as the nature of pain, multi-diagnosis, more than one site of pain, treatments, and general practitioner, but not the severity of pain and use of invasive treatments, had an impact on the choice of a pain clinic. Conclusion: Opioids are useful in managing moderate or severe chronic pain. Multimodal approaches are used for the management of chronic pain. Moreover, it is not clear how patients are addressed to access different pain clinics (spoke versus hub) networks. More widespread adoption is needed for an interdisciplinary approach to managing chronic pain and adopting guideline recommendations, and rigorous research is required to provide more substantial evidence and support clinical practice. [ABSTRACT FROM AUTHOR]

Current pharmacological treatment of diabetes is largely algorithmic. Other than for cardiovascular disease or renal disease, where sodium–glucose cotransporter 2 inhibitors and/or glucagon-like peptide-1 receptor agonists are indicated, the choice of treatment is based upon overall risks of harm or side effect and cost, and not on probable benefit. Here we argue that a more precise approach to treatment choice is necessary to maximise benefit and minimise harm from existing diabetes therapies. We propose a roadmap to achieve precision medicine as standard of care, to discuss current progress in relation to monogenic diabetes and type 2 diabetes, and to determine what additional work is required. The first step is to identify robust and reliable genetic predictors of response, recognising that genotype is static over time and provides the skeleton upon which modifiers such as clinical phenotype and metabolic biomarkers can be overlaid. The second step is to identify these metabolic biomarkers (e.g. beta cell function, insulin sensitivity, BMI, liver fat, metabolite profile), which capture the metabolic state at the point of prescribing and may have a large impact on drug response. Third, we need to show that predictions that utilise these genetic and metabolic biomarkers improve therapeutic outcomes for patients, and fourth, that this is cost-effective. Finally, these biomarkers and prediction models need to be embedded in clinical care systems to enable effective and equitable clinical implementation. Whilst this roadmap is largely complete for monogenic diabetes, we still have considerable work to do to implement this for type 2 diabetes. Increasing collaborations, including with industry, and access to clinical trial data should enable progress to implementation of precision treatment in type 2 diabetes in the near future. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological: n = 25; non-pharmacological: n = 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane's Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (n = 4) and Class II (n = 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference. [ABSTRACT FROM AUTHOR]

Hellenia speciosa (J.Koenig) S.R. Dutta is a plant species belonging to the family Costaceae. It is widely distributed in China, India, Malaysia, Indonesia, tropical, and subtropical Asia. In Ayurveda, the rhizome of this plant has been extensively used to treat fever, rash, asthma, bronchitis, and intestinal worms. The objective of the present study was to investigate the phytochemical constituents of the leaf of Hellenia speciosa using gas chromatography and mass spectroscopy analysis (GC-MS). The GC-MS analysis revealed the presence of 17 phytochemical components in the ethanolic leaf extract of Hellenia speciosa. The prevailing bioactive compounds present in Hellenia speciosa were thymol (RT-10.019; 3.59%), caryophyllene (RT-11.854; 0.62%), caryophyllene oxide (RT-13.919; 1.34%), artumerone (RT-14.795; 1.35%), hexadecanoic acid methyl ester (RT-17.536; 2.77%), 9,12-octadecanoic acid methyl ester (RT-19.163; 1.35%), squalene (RT-24.980; 1.19%), piperine (RT-25.745; 3.11%), beta tocopherol (RT-26.681; 2.88%), vitamin E (RT-27.290; 2.64%), progesterone (RT-29.608; 3.18%), caparratriene (RT-29.861; 9.72%), and testosterone (RT-30.73; 5.81%). The compounds were identified by comparing their retention time and peak area with that of the literature and by interpretation of mass spectra. The results and findings of the present study suggest that the plant leaf can be used as a valuable source in the field of herbal drug discovery. The presence of bioactive compounds justifies the use of plant leaves for treating various diseases with fewer side effects and recommended the plant of pharmaceutical importance. However, further studies are needed to undertake its bioactivity and toxicity profile. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods: MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects. Results: Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21–0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08–0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06–0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10–0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09–0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64–0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61–0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion: Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain. [ABSTRACT FROM AUTHOR]

New hydrazinylidene derivatives were synthesized under appropriate conditions and in excellent yields, by the reaction between a new [1,3]thiazolo[3,2-a]benzimidazol-2(3H)-one substrate and a series of aryldiazonium salts bearing groups with different electronic effect. The structures of the synthesized compounds were verified by FT-IR, 1H NMR and mass spectra. The pharmacological study including determining antimicrobial activity, cytotoxicity LD50 and histological study for compound ethyl 4-[(2Z)-2-(2-oxo[1,3]thiazolo[3,2-a] benzimidazol-3(2H)-ylidene)hydrazinyl]benzoate have been fulfilled. All chemical and biological result show possibility of using the compound ethyl 4-[(2Z)-2-(2-oxo[1,3]thiazolo[3,2-a] benzimidazol-3(2H)-ylidene)hydrazinyl]benzoate as a new topical antibiotic. [ABSTRACT FROM AUTHOR]

Background: Hunteria umbellate (K. Schum.) Hallier f. (Apocynaceae) is a tropical rainforest tree commonly found in sub-Saharan region of Africa. It is a useful and very popular plant among the locals due to the outstanding anti-diabetic activity of the seeds. Methods: A comprehensive literature search on articles published on phytochemical analysis and various pharmacological activities of Hunteria umbellate was carried out using search engines such as Google Scholar, PubMed and Science Direct. Results: In this review, it was deduced that H. umbellate is employed in folk medicine as an elixir for obesity, fever, leprosy sores, menstrual pain, infertility, yaws, intestinal worms, abdominal discomfort and stomach ache. Due to their durability and immunity against termites, the stems are coveted and desired as timbers in the construction of houses, while the bark has been reportedly exported to Europe for medicinal uses. Pharmacological activities such as fertility enhancing, aphrodisiac, hypoglycemic, anti-inflammatory, has been ascribed to the different morphological organs of H. umbellate. Moreover, compounds belonging to important classes of secondary metabolites with biological activities such as triterpenoids, flavonoids, tannins, alkaloids, quinic acids have been identified and characterized from the plant. Conclusion: From this review, it can be inferred that, numerous and bioactive principles with known biological usefulness are present in the extracts of H. umbellate and might be responsible for the observed biological and pharmacological activities. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN). Methods: A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review. Results: The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN. Discussion: Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer diagnosed in women. It is associated with multiple symptoms in both patients and caregivers, such as stress, anxiety, depression, sleep disturbance, and fatigue. Stress appears to promote cancer progression via activation of the sympathetic nervous system releasing epinephrine and norepinephrine as well as activation of hypothalamic-pituitary-adrenal axis releasing cortisol. These stress hormones have been shown to promote the proliferation of cancer cells. This review focuses on stress-reducing strategies which may decrease cancer progression by abrogating these pathways, with a main focus on the β-adrenergic signaling pathway. Patients utilize both non-pharmacologic and pharmacologic strategies to reduce stress. Non-pharmacologic stress-reduction strategies include complementary and alternative medicine techniques, such as meditation, yoga, acupuncture, exercise, use of natural products, support groups and psychology counseling, herbal compounds, and multivitamins. Pharmacologic strategies include abrogating the β2-adrenergic receptor signaling pathway to antagonize epinephrine and norepinephrine action on tumor and immune cells. β-Blocker drugs may play a role in weakening the pro-migratory and pro-metastatic effects induced by stress hormones in cancer and strengthening the anti-tumor immune response. Preclinical models have shown that non-selective β1/2-blocker use is associated with a decrease in tumor growth and metastases and clinical studies have suggested their positive impact on decreasing breast cancer recurrence and mortality. Thus, non-pharmacological approaches, along with pharmacological therapies part of clinical trials are available to cancer patients to reduce stress, and have promise to break the cycle of cancer and stress. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Recent Findings: Psychosis in Alzheimer’s disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Summary: Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets. [ABSTRACT FROM AUTHOR]

Astilbe rivularis Buch. Ham., a rhizomatous perennial herb of the Saxifragaceae family, has been listed in rare species. In traditional medicine the plant has been used for the treatment of ulcer, bleeding during child birth, inflammation, body ache, diarrhea, and dysentery. This article reviews and analyses the traditional use, pharmacological activities of the corresponding bioactive compounds, and toxicological data on A. rivularis species. A. rivularis has been used across Indian subcontinent to treat various human ailments. Its extract consists of alkaloids, flavonoids, coumarins and glycosides. These extracts as well as isolated bioactive compounds demonstrated various biological activities including antimicrobial, anti-peptic ulcer, anti-inflammatory, and antioxidant activity. Toxicological studies of the extract on brine shrimp larvae demonstrated mild toxicity; however no acute toxicity in mice. Although the pharmacological effect of A. rivularis has been poorly explored, the available data validated its use in ethnomedicine. To reveal the cryptic therapeutic potential of the species, research should focus on identification and mechanistic studies of the bioactive compounds. [ABSTRACT FROM AUTHOR]

Background: The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological.Aims: The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy.Methods: This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop’s score and caesarean delivery rate.Results: Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop’s score.Conclusions: Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas. [ABSTRACT FROM AUTHOR]

Background: Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system.Objective: To test the attenuation of the ketamine-induced BOLD signal by pretreatment with either a metabotropic glutamate receptor (mGluR) 2/3 or a mGluR2 agonist in healthy volunteersMethods: We used a ketamine challenge pharmacological magnetic resonance imaging (phMRI) paradigm to assess the modulatory effects of single acute doses of LY2140023 (pomaglumetad methionil), the methionine prodrug of the mGluR2/3 agonist LY404039 (10, 40, and 160 mg; N = 16 subjects) and of LY2979165, and the alanine prodrug of the selective orthosteric mGluR2 agonist 2812223 (20 and 60 mg; N = 16 subjects).Results: A reduction in the ketamine-evoked BOLD phMRI signal relative to placebo was observed at the highest doses tested of both LY2140023 and LY2979165. A relationship was observed between reduction of the BOLD signal and increasing plasma levels of 2812223 in the LY2979165 cohort.Conclusions: These results identify pharmacologically active doses of the group II mGluR agonist prodrugs LY2140023 and LY2979165 in humans. They also extend the classes of compounds that have been experimentally shown to reverse the ketamine-evoked phMRI signal in humans, further supporting the use of this method as a neuroimaging biomarker for assessing functional effects. [ABSTRACT FROM AUTHOR]

A review is done on the phytochemical profile and biological effects of Trichosanthes dioica Roxb. The findings suggest that this herb contains a number of important phytochemicals, which may link with its promising pharmacological activities such as antioxidant, anti-inflammatory, antimicorbial, anthelmintic, burn/wound healing, anti-cancer, anti-ulcer, anti-hypertensive, anti-diabetic, lipid lowering, neurological (anti-neuroinflammatory, anti-nociceptive and analgesic), gastro-protective, hepatoprotective, nephroprotective, cardio-protective, immunomodulatory, hair growth facilitatory and so on. With these, the clinical trial reports suggest that this herb can be used in the treatment of duodenal ulcer and skin disorder. Extracts from various parts of this herb and its derived compounds can be used to treat above-mentioned diseases/purposes, especially oxidative stress and its related diseases. More researches are highly appreciated to isolate and identify the active principles and their mechanisms of action of the biological activities. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes the recent literature and empirical studies on psychopharmacological approaches to treating female sexual interest/arousal disorder (FSIAD). Recent Findings: Several new drugs for FSIAD that are intended to increase sexual responsiveness by influencing central excitatory and inhibitory neuromodulatory processes are under development. Studies on flibanserin resulted in the first approved medication for the treatment of low sexual desire in premenopausal women. New drugs under development are testosterone combined with sildenafil or buspiron, bremelanotide, BP101, and nasal testosterone (TBS-2). Summary: Although pharmacological enhancement of sexual responsiveness may be potentially helpful in the treatment of FSIAD, the observed effects of flibanserin and other new drugs under development seem limited in terms of clinical significance. Given the multifactorial character of FSIAD, it may be important to integrate psychopharmacological treatment with sex therapy for optimal treatment efficacy. [ABSTRACT FROM AUTHOR]

In order to better understand the therapeutic mechanism of dual-function peptide 5rolGLP-HV in treatment of treat diabetes and its complication of thrombosis, the pharmacological effects and pharmacokinetic properties of 5rolGLP-HV were conducted in this study. 5rolGLP-HV was orally administered to diabetic mice, and the hypoglycemic mechanism was investigated. Thrombotic mice were applied to study the thrombus dissolving ability of 5rolGLP-HV. The concentration of rolGLP and rHV in rat plasma following single oral dose or intravenous injection of 5rolGLP-HV was measured. Treatment with 5rolGLP-HV decreased insulin resistance (2.96 ± 1.43 vs. 9.35 ± 1.51, p < 0.05) of diabetic mice. 5rolGLP-HV shortened the length of thrombus in thrombosis mice (2.92 ± 0.74 vs. 5.92 ± 1.16 cm, p < 0.01) and extended the thrombin time (15.35 ± 1.22 vs. 8.67 ± 0.89 s, p < 0.01) of normal mice. Meanwhile, 5rolGLP-HV restored the damage of pancreatic, liver, kidney, and adipose tissues induced in the diabetic mice. 5rolGLP-HV exhibited a fast absorption and slow elimination phase after digested into rolGLP-1 and rHV in vivo. These results suggested that 5rolGLP-HV had an ideal therapeutic potential in the prevention of β cell dysfunction in type 2 diabetes and delay of the thrombus. [ABSTRACT FROM AUTHOR]

Within the Ayurvedic medical tradition of India, Ashwagandha ( Withania somnifera) is a well-known herb. A large number of withanolides have been isolated from both its roots and its leaves and many have been assessed for their pharmacological activities. Amongst them, Withaferin A is one of its most bioactive phytoconstituents. Due to the lactonal steroid's potential to modulate multiple oncogenic pathways, Withaferin A has gained much attention as a possible anti-neoplastic agent. This review focuses on the use of Withaferin A alone, or in combination with other treatments, as a newer option for therapy against the most aggressive variant of brain tumors, Glioblastoma. We survey the various studies that delineate Withaferin A's anticancer mechanisms, its toxicity profiles, its pharmacokinetics and pharmacodynamics and its immuno-modulating properties. [ABSTRACT FROM AUTHOR]

This review paper was considered to find out the relationship, how to bring together traditional uses and modern pharmacological uses and provide a foundation for a more rigorous systemic investigation of ginseng. Ginseng is well-known worldwide as a medicinal plant. Its traditional and modern medicinal applications have been well documented. This medicinal plant is of great value to the people of Korea, China, and Japan and has been used for many purposes. Though all the parts of these plants have medicinal value, the roots are used most extensively in traditional medicine, especially for its curative and restorative properties. Ginseng is used to treat a variety of illnesses in traditional medicine. It is most effective for impotence, insomnia, anorexia, hypodynamia, diabetes, palpitation, shortness of breath, and hemorrhage. From a modern medical point of view, ginseng possesses a variety of constituents, including ginsenosides, polysaccharides, peptides, and polyacetylenic alcohols that have been used effectively for the central nervous system,neuroprotective, immunomodulatory, and anticancer effects. In particular, ginsenosides as an active ingredient have antioxidant, anti-inflammatory, antiapoptotic, and immunostimulant properties. The understanding of ginseng efficacy from Traditional Korean Medicine (TKM) and Traditional Chinese Medicine (TCM) can provide insights for modern chemical and pharmacological research. Such research will help clarify the pharmacodynamics and mechanisms of action of ginseng. [ABSTRACT FROM AUTHOR]

Rationale: There is a significant interest in the NMDA-receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. Pharmacological MRI in awake nonhuman primates provides a highly translational model for studying the brain network dynamics involved in producing these drug effects. Objective: The present study evaluated ketamine-induced changes in functional connectivity (FC) in awake rhesus monkeys. The effects of ketamine after pretreatment with the antipsychotic drug risperidone were also examined. Methods: Functional MRI scans were conducted in four awake adult female rhesus monkeys during sub-anesthetic i.v. infusions of ketamine (0.345 mg/kg bolus followed by 0.256 mg kg h constant infusion) with and without risperidone pretreatment (0.06 mg/kg). A 10-min window of stable BOLD signal was used to compare FC between baseline and drug conditions. FC was assessed in specific regions of interest using seed-based cross-correlation analysis. Results: Ketamine infusion induced extensive changes in FC. In particular, FC to the dorsolateral prefrontal cortex (dlPFC) was increased in several cortical and subcortical regions. Pretreatment with risperidone largely attenuated ketamine-induced changes in FC. Conclusions: The results are highly consistent with similar human imaging studies showing ketamine-induced changes in FC, as well as a significant attenuation of these changes when ketamine infusion is preceded by pretreatment with risperidone. The extensive increases shown in FC to the dlPFC are consistent with the idea that disinhibition of the dlPFC may be a key driver of the antidepressant and psychotomimetic effects of ketamine. [ABSTRACT FROM AUTHOR]

The aim of this present study is to investigate pharmacological activities of organic crude fractions of Dysophylla auricularia. For this organic fractions namely - ethanol, chloroform and n-hexane have been investigated for antimicrobial, anti-diarrheal, anti-inflammatory and membrane stabilization, α-glycosidase inhibitory and antipyretic activities. Results suggest that in the antimicrobial sensitivity study, ethanol and chloroform fractions produced inhibition zones with the ranges of 12 to 20 mm and 7 to 21 mm, respectively; where they strongly inhibited the growth of Shigella sonnei, Escherichia coli, Shigella dysenteriae and Microsporum sp. Crude fractions also revealed the presence of antidiarrheal, antiinflammatory and membrane stabilization, anti-amylase as well as antipyretic activities. In conclusion, it should be mentioned that D. auricularia may have one of the good sources for phytotherapy. [ABSTRACT FROM AUTHOR]

As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cell lines. Because of their similarities they are often treated as the same in experimental studies. However, there are many differences that have been largely over-sighted or ignored between them. In this review, we summarize the differences between HepG2 and Hep3B cell lines that can be found in the literature based on PubMed search. We particularly focus on the differential gene expression, differential drug responses (chemosensitivity, cell cycle and growth inhibition, and gene induction), signaling pathways associated with these differences, as well as the factors in governing these differences between HepG2 and Hep3B cell lines. Based on our analyses of the available data, we suggest that neither HBx nor p53 may be the crucial factor to determine the differences between HepG2 and Hep3B cell lines although HBx regulates the expression of the majority of genes that are differentially expressed between HepG2 and Hep3B. Instead, the different maturation stages in cancer development of the original specimen between HepG2 and Hep3B may be responsible for the differences between them. This review provides insight into the molecular mechanisms underlying the differences between HepG2 and Hep3B and help investigators especially the beginners in the areas of liver cancer research and drug metabolism to fully understand, and thus better use and interpret the data from these two cell lines in their studies. [ABSTRACT FROM AUTHOR]

Introduction: Approaches to the diagnosis and treatment of premature ejaculation (PE) have evolved over the past 50 years. In this paper, we briefly review significant historical and conceptual changes in the understanding of PE, with the aim of suggesting a contemporary integrative treatment plan. Methods: A review of PE diagnostic nosology, risk factors, and classical and contemporary treatment strategies suggests the need for an integrative approach so as to ensure both increased ejaculatory latency and relationship satisfaction. Results: A multi-faceted integrative treatment process is offered, emphasizing brevity and relying on a modified PLISSIT model. This model, summarized in a flow chart, progresses through sequentially deeper levels of engagement and includes attention to physiological, behavioral, cognitive-affective, and relationship factors, addressing each on an as needed basis. Conclusion: Important to any treatment model is consideration of time, cost, and access. The proposed model attempts to remove potential barriers for seeking treatment by addressing all three concerns. [ABSTRACT FROM AUTHOR]

Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful antineoplastic agent used routinely in firstline combination chemotherapy of testicular cancer, small-cell lung cancer and non-Hodgkin's lymphoma. Etoposide displays narrow therapeutic index, erratic pharmacokinetics and dose individualization that needs to be achieved for overcoming inter- and intra-patient variability (25-80%), so as to maintain proper drug exposure within a therapeutic range. Etoposide posses high plasma protein binding (97%) and is degraded via complex metabolic pathways. The main pharmacokinetic determinants of etoposide are still not completely defined in order to optimize the pharmaco-therapeutic parameters including dose, therapeutic schedule and route of administration. Much research has been done to determine drug-drug and herb-drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability of etoposide. [ABSTRACT FROM AUTHOR]

Since prehistoric era, plant-derived drugs were much preferred due to their less side effects than drugs of synthetic origin. Bioassay-guided selection of active fraction of a plant extract and further isolation and characterization of the pure bioactive compounds are in practice in both academic and industrial research. Zingiberaceae, a medicinally important, ornamental, monocotyledonous family has potential members in the tribe Alpinieae, among which the genus Alpinia is studied under this current review due to its wide range of biomedical applications. The members in the genus possess many bioactive compounds against harmful microbes to deadly diseases like cancer by regulating the different signalling pathway systems. Several compounds have been discovered and found to deliver diversified biological efficacy either in vitro or in vivo against a range of diseases. The chemical profiling of the genus and investigation of crude essential oils and individual bioactive compounds towards the therapeutic importance in various disciplines have been documented in the current review. [ABSTRACT FROM AUTHOR]

The genus Berberis is well known for its diversity and pharmacological uses in traditional medicine system since ancient time. Exploring this medicinal plant with more prominence is the need of present day medicinal system. The present review highlighted the phytochemical and pharmacological studies reported from genus Berberis over the last two decades. [ABSTRACT FROM AUTHOR]

Behavioral disturbances are frequently the most challenging manifestations of dementia and are exhibited in almost all people with dementia. Common behavioral disturbances can be grouped into four categories: mood disorders (e.g., depression, apathy, euphoria); sleep disorders (insomnia, hypersomnia, night-day reversal); psychotic symptoms (delusions and hallucinations); and agitation (e.g., pacing, wandering, sexual disinhibition, aggression). They are often persistent, greatly diminish quality of life of patients and their family caregivers, cause premature institutionalization, and pose a high economic burden on the patient, family, and society. Behavioral disturbances can be prevented and treated with a multifaceted approach that supports dignity and promotes comfort and quality of life of persons with dementia and their family members. Management involves prompt treatment of reversible factors and management of symptoms using primarily individualized nonpharmacological interventions. Pharmacological interventions need to be restricted to behavioral emergencies and for short-term treatment of behavioral disturbances that pose imminent danger to self or others. [ABSTRACT FROM AUTHOR]

Mechanisms underlying acquired nystagmus are better understood than those leading to infantile nystagmus. Accordingly, further progress has been made in the development of effective therapies for acquired nystagmus, mainly through pharmacological interventions. Some of these therapies have been developed under the guidance of findings from experimental animal models. Although mechanisms behind infantile nystagmus are less understood, progress has been made in determining the genetic basis of nystagmus and characterizing associated sensory deficits. Pharmacological, surgical, and other treatments options for infantile nystagmus are now emerging. Further investigations are required for all forms of nystagmus to produce high-quality evidence, such as randomized controlled trials, upon which clinicians can make appropriate treatment decisions. [ABSTRACT FROM AUTHOR]

Recent work regarding the analysis of brain imaging data has focused on examining functional connectivity of the brain. In this paper, we developed and applied a novel framework to examine the modulation of functional connectivity networks during resting state or experimental stimuli. Hierarchical clustering within anatomically parcellated brain regions is used to cluster voxels into anatomically local, functionally homogenous groups. Parcellation allows for the assessment of connectivity at a region of interest level, rather than a voxel-specific level. The framework utilizes a mixed-effects model of the Fisher Z-transformed correlation between pairs of spatially distinct brain regions to assess the modulation of, or differences in, connectivity networks across multiple sessions or between groups of patients. A permutation test was employed to control family-wise type I error. We applied our method to evaluate the effects of a non-selective opioid receptor antagonist, naloxone, on resting state functional connectivity networks with multi-session multi-subject ( n = 10) functional magnetic resonance imaging data. Naloxone induced a significant reduction in resting state connectivity between the right thalamus and the right parahippocampal gyrus when compared to saline solution. [ABSTRACT FROM AUTHOR]

Purpose of review: The goal of the current review is to provide an update on the management of agitation in persons with dementia with a focus on pharmacological management of persons with Alzheimer's disease. Recent findings: As consistently effective and safe pharmacologic interventions are still lacking, identifying and addressing medical and environmental precipitants remain a priority. Acetylcholinesterase inhibitors and memantine should be initiated to enhance cognition, and if present, management of insomnia or sundowning with trazodone is indicated. If agitation persists, treatment with citalopram can be initiated with attention paid to potential prolongation of the QT interval. Treatment with low doses of atypical antipsychotics such as risperidone or quetiapine can be effective after appropriate consideration of and disclosure of potential adverse effects. Summary: In light of the lack of consistently effective treatments for agitation in dementia, there have been renewed efforts to define the condition and improve the design of trials of medications to treat it. Considering the heterogeneity of patients and their comorbidities as well as the specific nature of their "agitation", there is no "one-size fits all" approach to agitation in AD. However, many options exist that can be prudently pursued for this common problem in this delicate population. [ABSTRACT FROM AUTHOR]