A Systematic Review and Meta-Analysis on Death Anxiety During COVID-19 Pandemic.

This systematic review was conducted to estimate the pooled score of death anxiety during the COVID-19 pandemic. All eligible articles from January 2020 to May 2022 reporting the death anxiety score were included in the analysis b.y searching the Scopus, PubMed, Embase, and ISI databases. The standard score of death anxiety in the COVID-19 pandemic was 50%. The highest score of death anxiety was related to patients with COVID-19 (59.4%), other chronic patients (58.9%), and the elderly (56.4%). The lowest death anxiety score was related to the general population (42.9%) and health care workers (48.2%). The death anxiety score in the studies whose data was collected in 2020 and 2021 was 51% and 62%, respectively. During the COVID-19 pandemic, people experienced high death anxiety, which had terrible effects on their lives. Therefore, it seems necessary to provide training courses to deal with death anxiety for other possible pandemics.

Feasibility and acceptability pilot of video-based direct observed treatment (vDOT) for supporting antitubercular treatment in South India: a cohort study.

OBJECTIVES: The objective of this study was to assess the feasibility and acceptability of video-based anti-tuberculosis (TB) treatment adherence support in patients with TB (PwTB) in South India. DESIGN: An exploratory cohort. SETTING: Participants were recruited at the TB treatment centre (direct observed treatment short centre) of a tertiary-level teaching facility in Bangalore, Karnataka, South India. PARTICIPANTS: The study enrolled 25 PwTB, with replacement. Adult PwTB who were on drug-sensitive treatment regimens were included, while those who had drug resistant TB were excluded from the study. INTERVENTION: Participants received scheduled adherence reminders and were trained to videorecord themselves swallowing their medication via a mobile application. The application was automated to submit these videos for evaluation. Participants were followed up monthly till treatment completion or withdrawal. OUTCOME MEASURES: Adherence rate and acceptability of video-based directly observed treatment (vDOT). RESULTS: The mean±SD age of the participants was 33±14 years, majority were females (16, 64%), residing in urban areas (24,96%), married (17, 68%) and had access to smart phones (23,92%). A total of 3193 person days of follow-up was completed; of the videos submitted within the first 6 months of enrollment (2501), 94% (2354/2501) were considered 'acceptable' and 16 (64%) participants were optimally adherent (ie, ≥80%). Participant videos improved in quality and a higher proportion met acceptability criteria over time. Twenty-one (84%) participants stated that they found the application easy to learn; 13 (52%) preferred vDOT over DOT. Mixed model logistic regression showed that those who are married are more likely have daily adherence to anti-TB treatment. CONCLUSION: Video-based mobile phone interventions are acceptable to PwTB and the ease of using the application increases with time. To provide patient-centred care, vDOT is a promising option that can be offered to patients for treatment support and adherence monitoring.

Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.

Effects of almond intake on oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: Several randomized controlled trials (RCTs) have shown that almonds can improve oxidative stress indices, but the results are controversial. Therefore, the goal of this research was to carry out a systematic review and meta-analysis of all RCTs that evaluated the effect of almonds on selected oxidative stress indices. METHODS: A systematic search was conducted up to April 2022 on PubMed, Scopus, Web of Science, and Google Scholar. We have selected the studies that investigated the effects of almonds on malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) levels in adults. Data were pooled by using the random-effects model. The risk of bias in individual studies was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Seven RCTs involving 424 participants were analyzed. The results indicated that almond intake led to a significant decrease in MDA levels (WMD: - 6.63 nmol/ml; 95 % CI: - 8.72 to - 4.54; P < 0.001). However, no significant effect was observed on Ox-LDL (Hedges' g: - 0.12; 95 % CI: - 0.34 to 0.10; P = 0.28). Sensitivity analysis showed that overall estimates were not affected by the elimination of any study. We did not observe any evidence regarding publication bias. CONCLUSION: The present meta-analysis suggests that almond intake can improve MDA levels and might play a beneficial role in the reinforcement of the antioxidant defense system and amelioration of oxidative stress in adults. There is a need for more studies with larger groups to better estimate this effect.

Tumor-associated Macrophages (TAMs) in Cancer Resistance; Modulation by Natural Products.

Tumor-associated macrophages (TAMs) play a pivotal role in the progression and resistance of tumors to different anticancer drugs. TAMs can modulate the tumor microenvironment (TME) in favor of immune system exhaustion. The interactions of TAMs with TME can affect the function of cytotoxic CD8+ T lymphocytes (CTLs) and natural killer (NK) cells. Furthermore, TAMs can induce cancer cell proliferation by releasing some growth factors, such as transforming growth factor (TGF)-ß. TAMs have several positive cross-talks with other immune suppressive cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), cancerassociated fibroblasts (CAFs), and cancer cells, leading to the release of growth factors, the proliferation of cancer cells and tumor growth. These interactions also can induce invasion and migration of cancer cells, angiogenesis, and metastasis. The inhibition of TAMs is an intriguing strategy for overcoming tumor resistance and suppression of cancer cells. Some natural-derived agents such as melatonin, curcumin, resveratrol, apigenin, and other flavonoids have shown the ability to modulate TME, including TAMs. These adjuvants may be able to boost antitumor immunity through the modulation of TAMs. This review explains the modulatory effects of some well-known naturally derived agents on the activity of TAMs. The modulation of TAMs by these agents may be useful in suppressing tumor growth and invasion.

Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck: A Tertiary Cancer Center Experience.

Apurva A. PatelAnanya PareekBackground Immunotherapy is a proven therapeutic option in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum therapy. At present, there are no published Indian data regarding administration of nivolumab in this setting. Aim The aim of this study is to retrospectively evaluate the efficacy and toxicity of nivolumab in R/M HNSCC among Indian patients who progressed after one or more lines of chemotherapy, including platinum agents. Methods All patients of R/M HNSCC who received nivolumab between 2/6/2018 to 31/3/2020 were assessed retrospectively for the efficacy and toxicity of nivolumab therapy. Statistical Analysis All the data analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Descriptive analysis was performed to obtain baseline characteristic of the study sample. Survival analysis was done using the Kaplan-Meier method. Results Nivolumab therapy was tolerated well, with no new safety concerns, except one (8.3%) patient experienced grade ¾ toxicity (gastrointestinal). The clinical benefit rate (CBR) was found to be 66.7%. The median progression-free survival (PFS) was 3 months (95% CI; 2.093-3.907), and median overall survival (OS) was 8 months (95% CI; 3.731-12.269) from the date of first dose of nivolumab. Conclusions In our study, efficacy and toxicity were comparable with international data with no new safety concerns. Nivolumab emerged as an astonishing treatment option with tolerable toxicity profile in patients with R/M HNSCC postplatinum therapy, although limited treatment options are available at present.

Synthesis, DNA binding ability and anticancer activity of 2-heteroaryl substituted benzimidazoles linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of <10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.

An overview of phenylcyclopropylamine derivatives: biochemical and biological significance and recent developments.

trans-2-Phencylcyclopropylamine (2-PCPA), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases (MAOs). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2-PCPA also affects depression-associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABAB receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 (CYP) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2-PCPA has attracted interest as a structural scaffold for the development of mechanism-based inhibitors of various enzymes, including lysine-specific demethylase 1 (LSD1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2-PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure-activity relationships (SAR), biological and biochemical properties, and mechanism of actions of 2-PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects.

Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors.

Selective inhibitors of human sirtuin 2 (SIRT2), a deacetylase, are candidate therapeutic agents for neurodegenerative diseases such as Parkinson's disease and Huntington's disease as well as potential tools for elucidating the biological functions of SIRT2. On the basis of homology models of SIRT1 and SIRT2, we designed and prepared a series of 2-anilinobenzamide analogues. Enzyme assays using recombinant SIRT1 and SIRT2 revealed that 3'-phenethyloxy-2-anilinobenzamide analogues such as 33a and 33i are potent and selective SIRT2 inhibitors, showing more than 3.5-fold greater SIRT2-inhibitory activity and more than 35-fold greater SIRT2-selectivity compared with AGK2 (3), a previously reported SIRT2-selective inhibitor. Compound 33a also induced a dose-dependent selective increase of α-tubulin acetylation in human colon cancer HCT116 cells, indicating selective inhibition of SIRT2 in the cells. These 3'-phenethyloxy-2-anilinobenzamide derivatives represent an entry into a new class of SIRT2-selective inhibitors.

Recent advances on structural modifications of benzothiazoles and their conjugate systems as potential chemotherapeutics.

INTRODUCTION: Benzothiazole scaffold comprises a bicyclic ring system and is known to exhibit a wide range of biological properties including antimicrobial and anticancer activities. Benzothiazole derivatives have long been therapeutically used for the treatment of various diseases. However, in recent years, 2-arylbenzothiazoles have emerged as an important pharmacophore in the development of antitumor agents. The promising biological profile and synthetic accessibility have been attractive in the design and development of new benzothiazoles and their conjugate systems as potential chemotherapeutics. AREAS COVERED: This review mainly focuses on the structural modifications of benzothiazole scaffold, development of various series of benzothiazoles and their conjugates as new antitumor agents. Furthermore, heterocyclic derivatives bearing benzothiazole moiety and their in vitro as well as in vivo screening, structure-activity relationships (SAR), mechanism, pharmacokinetics, clinical use and their future therapeutic applications are discussed here. EXPERT OPINION: A large number of benzothiazole derivatives discussed here possess potent anticancer activity and can be further developed as drug candidates. Benzothiazole conjugates could also display synergistic effect and still there is a need to use the drug combinations permitting lower dose and development of new generation of drugs. Despite encouraging results that have been observed for their response to tumor in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer. We believe that this review gives a better understanding and scope for future drug design and development of benzothiazole-based compounds to implicate their use in cancer chemotherapy.

Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor.

Optically active (1S,2R)-NCL-1 and (1R,2S)-NCL-1 were synthesized and evaluated for their lysine-specific demethylase 1 inhibitory activity and cell growth inhibitory activity. In enzyme assays, the (1S,2R)-isomer was approximately four times more potent than the (1R,2S)-isomer. In cell growth inhibition assays, the two isomers showed similar activity in HEK293 cells and SH-SY5Y cells, whereas the (1S,2R)-isomer showed approximately four times more potent activity than the (1R,2S)-isomer in HeLa cells.

Cyclooxygenase inhibitors: scope of their use and development in cancer chemotherapy.

The traditional nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibition of cyclooxygenase-1 (COX-1) as well as COX-2 enzymes. As COX-1 is responsible for maintaining normal biological functions, the nonselective inhibition of these enzymes caused side effects including gastrointestinal (GI) problems. Recently developed selective COX-2 inhibitors could reduce these adverse effects, but the evidence of cardiovascular side effects including an increased risk of myocardial infarction began to emerge, and some of the COX-2 inhibitors were eventually withdrawn from the market and this led to the downfall of this research. So, the discovery of novel COX-2 inhibitors with their safety profile became the biggest challenge in pharmaceutical research. However, recent mechanistic and clinical studies revolutionized this area by indicating the fact that COX-2 is involved in apoptosis resistance, angiogenesis, and tumor progression. Epidemiological data suggest that selective COX-2 inhibitors might prevent the development of cancers. Moreover, COX-2 is found to be overexpressed in many cancers thus making it an attractive therapeutic target for the prevention and treatment of a number of malignancies. The purpose of this review is to focus on the medicinal chemistry aspects of COX-2 inhibitors in cancer chemotherapy and recent reports on these inhibitors as anticancer agents. We attempted to cover only the COX inhibitors that showed anticancer activity, although a number of potent COX-2 inhibitors have been reported without their anticancer effects. Furthermore, structure-activity relationships (SAR) of different classes of compounds for COX-2 inhibition as well as anticancer activity, and their future applications are discussed.

Synthesis and biological evaluation of mercapto triazolo-benzothiadiazine linked aminobenzothiazoles as potential anticancer agents.

The synthesis of a series of 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[4,3-b][1,2,4]benzothiadiazine coupled with sulfanylacetamido benzothiazole pharmacophores (5a-g) is described. All the synthesized compounds have been evaluated for their anticancer activity. Most of the compounds showed significant growth inhibitory activity against selected human tumor cell lines. Interestinlgy, one of the synthesized compounds 5d, exhibited GI(50) values of 1.4 and 2.1 microM against RPMI-8226 (leukemia) and HOP-62 (lungs) cell lines, respectively.