Experimental and theoretical validation for transmutation of palladium at electrochemical interfaces.

Electrolysis of DO may be used as a portable neutron source with numerous applications without the complexity of huge reactor operations. Herein, we report reproducible fast neutron generation by electrolysis of DO using palladium cathode and platinum anode, which was detected with diamond detector, gas filled He detectors after thermalisation with high density polythene, as well as novel epoxy resin and CR-39 detectors. Notably, a highly reproducible neutron generation at electrochemical surfaces of palladium electrode was observed and signature transmutation via Pd (d, n) Ag was corroborated.

A BODIPY-Naphtholimine-BF Dyad for Precision Photodynamic Therapy, Targeting, and Dual Imaging of Endoplasmic Reticulum and Lipid Droplets in Cancer.

Currently, effective therapeutic modalities for pancreatic ductal adenocarcinoma (PDAC) are quite limited, leading to gloomy prognosis and ∼6-months median patient survival. Recent advances showed the promise of photodynamic therapy (PDT) for PDAC patients. Next generation photosensitizers (PS) are based on "organelle-targeted-PDT" and provide new paradigm in the field of precision medicines to address the current challenge for treating PDAC.

Recent advancement of autophagy in polyploid giant cancer cells and its interconnection with senescence and stemness for therapeutic opportunities.

Recurrent chemotherapy-induced senescence and resistance are attributed to the polyploidization of cancer cells that involve genomic instability and poor prognosis due to their unique form of cellular plasticity. Autophagy, a pre-dominant cell survival mechanism, is crucial during carcinogenesis and chemotherapeutic stress, favouring polyploidization. The selective autophagic degradation of essential proteins associated with cell cycle progression checkpoints deregulate mitosis fidelity and genomic integrity, imparting polyploidization of cancer cells.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment.

Emerging roles of lysosome homeostasis (repair, lysophagy and biogenesis) in cancer progression and therapy.

In the era of personalized therapy, precise targeting of subcellular organelles holds great promise for cancer modality. Taking into consideration that lysosome represents the intersection site in numerous endosomal trafficking pathways and their modulation in cancer growth, progression, and resistance against cancer therapies, the lysosome is proposed as an attractive therapeutic target for cancer treatment. Based on the recent advances, the current review provides a comprehensive understanding of molecular mechanisms of lysosome homeostasis under 3R responses: Repair, Removal (lysophagy) and Regeneration of lysosomes.

SIRT1 inhibits mitochondrial hyperfusion associated mito-bulb formation to sensitize oral cancer cells for apoptosis in a mtROS-dependent signalling pathway.

SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III histone deacetylase acting as a tumor suppressor gene, is downregulated in oral cancer cells. Non-apoptotic doses of cisplatin (CDDP) downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks.

In house synthesized novel distyryl-BODIPY dye and polymer assembly as deep-red emitting probe for protamine detection.

In this contribution, we designed and synthesized a deep-red emitting distyryl-BODIPY dye (dye 3) which is non-fluorescent in aqueous solution due to the formation of non-emissive aggregates. However, in presence of an amphiphilic polymer (polystyrene sulfonate, PSS), the aggregated dye molecules de-aggregate and form dye 3-PSS complex, which significantly modulates the optical features of the bound dye. Interestingly, the dye 3-PSS complex shows turn-on fluorescence response in deep-red region in presence of protamine (Pr) due to the formation of dye 3-PSS-Pr ternary complex.

Design, synthesis and development of a dual inhibitor of Topoisomerase 1 and poly (ADP-ribose) polymerase 1 for efficient killing of cancer cells.

Combinatorial inhibition of Topoisomerase 1 (TOP1) and Poly (ADP-ribose) polymerase 1 (PARP1) is an attractive therapeutic strategy which is under active investigation to address chemoresistance to TOP1 inhibitors. However, this combinatorial regimen suffers from severe dose limiting toxicities. Dual inhibitors often offer significant advantages over combinatorial therapies involving individual agents by minimizing toxicity and providing conducive pharmacokinetic profiles.

Functional inhibition of RECQL5 helicase elicits non-homologous end joining response and sensitivity of breast cancers to PARP inhibitor.

Poly (ADPRibose) Polymerase inhibitor (PARPi) are clinically approved for the treatment of BRCA-mutated hereditary breast and ovarian cancers with homologous recombination (HR) deficiency, based on synthetic lethality concept. However, ∼90% of breast cancers are BRCA-wild type; they repair PARPi mediated damage through HR, leading to intrinsic de novo resistance. Hence, there is an unmet need of exploring novel targets in HR-proficient aggressive breast cancers for PARPi treatment.

Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer.

Designing heavy-atom-free triplet photosensitizers (PSs) is a challenge for the efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) with an efficient intersystem crossing (ISC) that is proportional to their twisting angle. But their difficult syntheses and weak absorption profile in the visible spectral region restrict their use as heavy-atom-free triplet PSs for PDT.

The inner mitochondrial membrane fission protein MTP18 serves as a mitophagy receptor to prevent apoptosis in oral cancer.

MTP18 (also known as MTFP1), an inner mitochondrial membrane protein, plays a vital role in maintaining mitochondrial morphology by regulating mitochondrial fission. Here, we found that MTP18 functions as a mitophagy receptor that targets dysfunctional mitochondria into autophagosomes for elimination. Interestingly, MTP18 interacts with members of the LC3 (also known as MAP1LC3) family through its LC3-interacting region (LIR) to induce mitochondrial autophagy.

Fluorogenic gemcitabine based light up sensor for serum albumin detection in complex biological matrices.

Herein we report fluorogenic derivative of gemcitabine (GEM-DNS), synthesized from gemcitabine hydrochloride and dansyl chloride in a single step. Owing to its large stoke shift of ∼200 nm and intriguing photophysical properties, the said dye has been utilized to estimate albumin concentration in complex bio-media such as human urine and blood serum. High sensitivity and selectivity towards albumin make the aforementioned dye a powerful diagnostic tool to detect ailments such as liver cirrhosis, diabetes, hypertension etc.

MTP18 inhibition triggers mitochondrial hyperfusion to induce apoptosis through ROS-mediated lysosomal membrane permeabilization-dependent pathway in oral cancer.

Although stress-induced mitochondrial hyperfusion (SIMH) exerts a protective role in aiding cell survival, in the absence of mitochondrial fission, SIMH drives oxidative stress-related induction of apoptosis. In this study, our data showed that MTP18, a mitochondrial fission-promoting protein expression, was increased in oral cancer. We have screened and identified S28, a novel inhibitor of MTP18, which was found to induce SIMH and subsequently trigger apoptosis.

Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer.

Mutation in Werner (WRN) RECQL helicase is associated with premature aging syndrome (Werner syndrome, WS) and predisposition to multiple cancers. In patients with solid cancers, deficiency of the WRN RECQL helicase is paradoxically associated with enhanced overall survival in response to treatment with TOP1 inhibitors, which stabilize pathological TOP1-DNA-covalent-complexes (TOP1cc) on the genome. However, the underlying mechanism of WRN in development of chemoresistance to TOP1 inhibitors is not yet explored.

Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study.

The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication.

Carbon nano-dot for cancer studies as dual nano-sensor for imaging intracellular temperature or pH variation.

Cellular temperature and pH govern many cellular physiologies, especially of cancer cells. Besides, attaining higher cellular temperature plays key role in therapeutic efficacy of hyperthermia treatment of cancer. This requires bio-compatible, non-toxic and sensitive probe with dual sensing ability to detect temperature and pH variations.

Synthesis of Bioactive Diarylheptanoids from and Their Mechanism of Action for Anticancer Properties in Breast Cancer Cells.

An efficient synthesis of the -derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone () and an α,β-unsaturated ketone () was developed starting from commercially available eugenol. Among these, compound showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells.

Pharmacological targeting of differential DNA repair, radio-sensitizes WRN-deficient cancer cells in vitro and in vivo.

Werner (WRN) expression is epigenetically downregulated in various tumors. It is imperative to understand differential repair process in WRN-proficient and WRN-deficient cancers to find pharmacological targets for radio-sensitization of WRN-deficient cancer. In the current investigation, we showed that pharmacological inhibition of CHK1 mediated homologous recombination repair (HRR), but not non-homologous end joining (NHEJ) repair, can causes hyper-radiosensitization of WRN-deficient cancers.

Targeting RECQL5 Functions, by a Small Molecule, Selectively Kills Breast Cancer o and .

Clinical and preclinical data reveal that RECQL5 protein overexpression in breast cancer was strongly correlated with poor prognosis, survival, and therapeutic resistance. In the current investigation, we report design, synthesis, and specificity of a small molecule, , which can preferentially kill RECQL5-expressing breast cancers but not RECQL5 knockout. Our stringent analysis showed that compound specifically sensitizes RECQL5-expressing cancers, while it did not have any effect on other members of DNA RECQL-helicases.

Dysregulation of mitophagy and mitochondrial homeostasis in cancer stem cells: Novel mechanism for anti-cancer stem cell-targeted cancer therapy.

Despite the potential of cancer medicine, cancer stem cells (CSCs) associated with chemoresistance and disease recurrence are the significant challenges currently opposing the efficacy of available cancer treatment options. Mitochondrial dynamics involving the fission-fusion cycle and mitophagy are the major contributing factors to better adaptation, enabling CSCs to survive and grow better under tumour micro-environment-associated stress. Moreover, mitophagy is balanced with mitochondrial biogenesis to maintain mitochondrial homeostasis in CSCs, which are necessary for the growth and maintenance of CSCs and regulate metabolic switching from glycolysis to oxidative phosphorylation.

Targeting autophagy reverses de novo resistance in homologous recombination repair proficient breast cancers to PARP inhibition.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) target tumours defective in homologous recombination (HR). Most BRCA-wild-type (WT) HR-proficient breast cancers are intrinsically resistant to PARP inhibitors, e.g.

Is DAPI assay of cellular nucleic acid reliable in the presence of protein aggregates?

DAPI is used extensively to identify and quantify DNA in cellular systems assuming its exclusive staining of nucleic acids. However, the present results show that DAPI has much higher affinity towards protein aggregates than DNA. Thus, the use of DAPI for the nucleic acid assay of cellular systems with protein aggregates may not be very reliable.

Thiol antioxidants sensitize malabaricone C induced cancer cell death via reprogramming redox sensitive p53 and NF-κB proteins in vitro and in vivo.

Specific focus on "redox cancer therapy" by targeting drugs to redox homeostasis of the cancer cells is growing rapidly. Recent clinical studies showed that N-acetyl cysteine (NAC) treatment significantly decreased the metabolic heterogeneity and reduced Ki67 (a proliferation marker) with simultaneous enhancement in apoptosis of tumor cells in patients. However, it is not yet precisely known how thiol antioxidants enhance killing of cancer cells in a context dependent manner.

Salinomycin reduces growth, proliferation and metastasis of cisplatin resistant breast cancer cells via NF-kB deregulation.

Cisplatin (cis-diamminedichloro-platinum, CDDP), is a widely used platinum compound for various solid tumors including breast cancer as first line of therapy. However, its positive effects are limited due to acquired drug resistance and severe side effects in non-malignant tissue, especially due to dose-dependent nephro- and/or neuro-toxicity. Salinomycin is an antibiotic with coccidiostat effect and has shown anticancer efficacy against various cancer cells with selectivity in targeting cancer stem cells.