Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

Burden of Chronic Nonhealing Wounds: An Overview of the Worldwide Humanistic and Economic Burden to the Healthcare System.

Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.

Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands.

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

Polypyridyl-based Co(III) complexes of vitamin B6 Schiff base for photoactivated antibacterial therapy.

Herein, five novel polypyridyl-based Co(III) complexes of Schiff bases, viz., [Co(dpa)(L1)]Cl (1), [Co(dpa)(L2)]Cl (2), [Co(L3)(L2)]Cl (3), [Co(L3)(L1)]Cl (4), and [Co(L4)(L1)]Cl (5), where dpa (dipicolylamine) = bis(2-pyridylmethyl)amine; H2L1 = (E)-2-((2-hydroxybenzylidene)amino)phenol; H2L2 = (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol; L3 = 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy); and L4 = 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy), were synthesized and characterized. Complexes 1, 3, and 4 were structurally characterized by single-crystal XRD, indicating an octahedral CoIIIN4O2 coordination core. The absorption bands of these complexes were observed in the visible range with a λmax at ∼430-485 nm. Complex 5 displayed an extra absorption band near 545 nm because of a ferrocene moiety. These absorptions in the visible region reflect the potential of the complexes to act as visible-light antimicrobial photodynamic therapy (aPDT) agents. All of these complexes showed reactive oxygen species (ROS)-mediated antibacterial effects against S. aureus (Gram-positive) and E. coli (Gram-negative bacteria) upon low-energy visible light (0.5 J cm-2, 400-700 nm) exposure. Additionally, 1-5 did not show any toxicity toward A549 (Human Lung adenocarcinoma) cells, reflecting their selective bacteria-killing abilities.

Polypyridyl CoII -Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents.

Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.

Cyanine-Functionalized 2,2'-Bipyridine Compounds for Photocatalytic Cancer Therapy.

Recently, interest has been given to developing photocatalytic anticancer drugs. This area of research is dominated by metal complexes. Here, we report the potential of lysosome/mitochondria targeting cyanine appended bipyridine compounds as the organic photocatalytic anticancer agents. The organocatalyst (bpyPCN) not only exhibits light-induced NADH oxidation but also generates intracellular ROS to demonstrate anticancer activity. This is the first example of organic compound induced catalytic NADH photo-oxidation in an aqueous solution and in cancer cells.

Metal Complexes for Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT) for cancer treatment is gaining attention owing to its non-invasive property and ultrasound's (US) deep tissue penetration ability. In SDT, US activates the sonosensitizer at the target deep-seated tumors to generate reactive oxygen species (ROS), which ultimately damage tumors. However, drawbacks such as insufficient ROS production, aggregation of sonosensitizer, off-target side effects, etc., of the current organic/nanomaterial-based sonosensitizers limit the effectiveness of cancer SDT. Very recently, metal complexes with tunable physiochemical properties (such as sonostability, HOMO to LUMO energy gap, ROS generation ability, aqueous solubility, emission, etc.) have been devised as effective sonosensitizers, which could overcome the limitations of organic/nanomaterial-based sonosensitizers. This concept introduces all the reported metal-based sonosensitizers and delineates the prospects of metal complexes in cancer sonodynamic therapy. This new concept of metal-based sonosensitizer can deliver next-generation cancer drugs.

Determinants of COVID-19 Breakthrough Infections and Severity in ChAdOx1 nCoV-19-Vaccinated Priority Groups.

The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ≤ 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease-mainly asthma-had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored.

Combination of Immunotherapy and Photo-pyroptosis as Novel Anticancer Strategy.

Immunotherapy has made great progress in clinical cancer treatment in recent years, but its therapeutic efficacy is significantly limited by the lack of immunogenicity in the tumor microenvironment. Pyroptosis is a type of programmed cell death in which the dying cancer cells produce inflammatory cytokines to relieve the immuno-suppressive microenvironment and thus increase anti-tumor immunity. Reactive oxygen species (ROS) produced during photodynamic therapy (PDT) are one of the efficient activators that induce pyroptosis. Recently, a few photosensitizers have emerged with the ability to induce immunogenic cancer cell death via pyroptosis, opening a new field for PDT. This highlight introduces the latest research on antitumor strategies achieved by the combination of immunotherapy and photodynamic therapy through photo-pyroptosis.

Os(II) complexes for catalytic anticancer therapy: recent update.

The recent dramatic enhancement in cancer-related mortality and the drawbacks (side effects and resistance) of Pt-based first-generation chemotherapeutics have escalated the need for new cancer medicines with unique anticancer activities for better human life. To overcome the demerits of Pt-based cancer drugs, the concept of catalytic anticancer agents has recently been presented in the field of anticancer metallodrug development research. Many intracellular transformations in cancer cells are catalyzed by metal complexes, including pyruvate reduction to lactate, NAD(P)+ reduction to NAD(P)H and vice versa, and the conversion of 3O2 to reactive oxygen species (ROS). These artificial in-cell changes with non-toxic and catalytic dosages of metal complexes have been shown to disrupt several essential intracellular processes which ultimately cause cell death. This new approach could develop potent next-generation catalytic anticancer drugs. In this context, recently, several 16/18 electron Os(II)-based complexes have shown promising catalytic anticancer activities with unique anticancer mechanisms. Herein, we have delineated the catalytic anticancer activity of Os(II) complexes from a critical viewpoint. These catalysts are reported to induce the in-cell catalytic transfer hydrogenation of pyruvate and important quinones to create metabolic disorder and photocatalytic ROS generation for oxidative stress generation in cancer cells. Overall, these Os(II) catalysts have the potential to be novel catalytic cancer drugs with new anticancer mechanisms.

A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India.

BACKGROUND: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India. METHODS: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed. FINDINGS: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism. INTERPRETATION: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings. FUNDING: No funding support.

Relationship of socio-economic inequality and overweight with non-communicable diseases risk factors: A study on underprivileged population.

BACKGROUND: Out of every five deaths in India three are due to Non-Communicable Diseases (NCDs). Two major modifiable risk factors for NCDs are overweight and socioeconomic inequality. This study assesses the burden of various NCDs risk factors and their relationship with socioeconomic inequality and overweight among the underprivileged population. AIM: To compare the different Non-Communicable Diseases risk factors with socioeconomic inequality and overweight. To evaluate the relationship between socioeconomic inequality and body weight with NCDs. MATERIALS AND METHODS: A cross-sectional study incorporating 241 random sample of participants was assessed using WHO Stepwise approach to NCD risk factor surveillance. Anthropometric measurements and biochemical analysis of 12 h of fasting venous blood samples were done. Data were analyzed using Stata version 16 and Graph Pad Prism 8, using two-sided significance tests at the 5% significance level. RESULTS: The study finds a 10-fold higher risk of tobacco use ( AOR = 10.18, C.I = 2.79 - 37.10) and 5 times higher risk of alcohol use AOR = 5.57, C.I = 1.25 - 24.65) among people with poor SES compared to higher SES. A significant correlation was observed between BMI, LDL cholesterol ( r = -16.0; P = 0.009) and HDL cholesterol (r = 18.0;P = 0.006) with socioeconomic status. The study finds that for individuals who were overweight the odds of systolic blood pressure (AOR = 2.11, C.I = 1.03-4.31), fasting blood sugar (AOR = 3.84, C.I = 1.30 -11.32), triglyceride level, (AOR = 2.20, C.I = 1.18 - 4.09) high-density lipoprotein ( AOR = 2.63, C.I = 1.26 - 5.46) were significantly higher compared to normal BMI individuals. CONCLUSION: The study showed that the socioeconomic patterning of the population is significantly associated with NCD risk factors. Obesity was closely linked with several major NCD risk factors.