Lipidomic Profiling in Cancer: Phospholipid Alterations and their Role in Tumor Progression.

Phospholipids play a crucial role in various aspects of cancer biology, including tumor progression, metastasis, and cell survival. Recent studies have highlighted the signifi-cance of phospholipid metabolism and signaling in multiple cancer types, such as breast, cer-vical, prostate, bladder, colorectal, liver, lung, melanoma, mesothelioma, and oral cancer. Al-terations in phospholipid profiles, particularly in phosphatidylcholine and phosphatidylethan-olamine, have been identified as potential biomarkers for cancer diagnosis and prognosis.

SMAC/DIABLO: A Guardian Angel in Boosting Anticancer Drug-Induced Apoptosis.

Apoptosis is an established hallmark of cancer. In normal conditions, apoptosis is strictly controlled; however, when it is not properly managed, it causes several complications, including cancer progression and drug resistance. SMAC/ Diablo (SMAC) is a mitochondrial protein that is released into the cytosol upon activation of BAX/BAK channels with apoptotic signals.

The Present State and Potential Applications of Artificial Intelligence in Cancer Diagnosis and Treatment.

An aberrant increase in cancer incidences has demanded extreme attention globally despite advancements in diagnostic and management strategies. The high mortality rate is concerning, and tumour heterogeneity at the genetic, phenotypic, and pathological levels exacerbates the problem. In this context, lack of early diagnostic techniques and therapeutic resistance to drugs, sole awareness among the public, coupled with the unavailability of these modern technologies in developing and low-income countries, negatively impact cancer management.

Correction: Pittala et al. The VDAC1-based R-Tf-D-LP4 Peptide as a Potential Treatment for Diabetes Mellitus. 2020, , 481.

In the original publication [...

Stem Cells as a Novel Source for Regenerative Medicinal Applications in Alzheimer's Disease: An Update.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded Aβ and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.

Role of Cytochrome P450 3A4 in Cancer Drug Resistance: Challenges and Opportunities.

One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications.

Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.

Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa.

Silencing the Mitochondrial Gatekeeper VDAC1 as a Potential Treatment for Bladder Cancer.

The strategy for treating bladder cancer (BC) depends on whether there is muscle invasion or not, with the latter mostly treated with intravesical therapy, such as with bacillus Calmette-Guérin (BCG). However, BCG treatment is unsuccessful in 70% of patients, who are then subjected to radical cystectomy. Although immune-checkpoint inhibitors have been approved as a second-line therapy for a subset of BC patients, these have failed to meet primary endpoints in clinical trials.

Interaction of SMAC with a survivin-derived peptide alters essential cancer hallmarks: Tumor growth, inflammation, and immunosuppression.

Second mitochondrial-derived activator of caspase (SMAC), also known as direct inhibitor of apoptosis-binding proteins with low pI (Diablo), is known as a pro-apoptotic mitochondrial protein released into the cytosol in response to apoptotic signals. We recently reported SMAC overexpression in cancers as essential for cell proliferation and tumor growth due to non-apoptotic functions, including phospholipid synthesis regulation. These functions may be associated with its interactions with partner proteins.

Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery-An Update.

Malaria continued to be a deadly situation for the people of tropical and subtropical countries. Although there has been a marked reduction in new cases as well as mortality and morbidity rates in the last two decades, the reporting of malaria caused 247 million cases and 619000 deaths worldwide in 2021, according to the WHO (2022). The development of drug resistance and declining efficacy against most of the antimalarial drugs/combination in current clinical practice is a big challenge for the scientific community, and in the absence of an effective vaccine, the problem becomes worse.

Pro-Apoptotic and Anti-Cancer Activity of the Vernonanthura Nudiflora Hydroethanolic Extract.

The mitochondrial voltage-dependent anion channel 1 (VDAC1) protein is involved in several essential cancer hallmarks, including energy and metabolism reprogramming and apoptotic cell death evasion. In this study, we demonstrated the ability of hydroethanolic extracts from three different plants, (Vern), (Bac), and (Pla), to induce cell death. We focused on the most active Vern extract.

Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer's disease protects against mitochondrial dysfunction and mitigates brain pathology.

Background: Alzheimer's disease (AD) exhibits mitochondrial dysfunctions associated with dysregulated metabolism, brain inflammation, synaptic loss, and neuronal cell death. As a key protein serving as the mitochondrial gatekeeper, the voltage-dependent anion channel-1 (VDAC1) that controls metabolism and Ca homeostasis is positioned at a convergence point for various cell survival and death signals. Here, we targeted VDAC1 with VBIT-4, a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity, and mitochondria dysfunction.

Naringin Attenuates the Diabetic Neuropathy in STZ-Induced Type 2 Diabetic Wistar Rats.

The application of traditional medicines for the treatment of diseases, including diabetic neuropathy (DN), has received great attention. The aim of this study was to investigate the ameliorative potential of naringin, a flavanone, to treat streptozotocin-induced DN in rat models. After the successful induction of diabetes, DN complications were measured by various behavioral tests after 4 weeks of post-induction of diabetes with or without treatment with naringin.

Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression.

Mitochondrial SMAC/Diablo induces apoptosis by binding the inhibitor of apoptosis proteins (IAPs), thereby activating caspases and, subsequently, apoptosis. Previously, we found that despite its pro-apoptotic activity, SMAC/Diablo is overexpressed in cancer, and demonstrated that in cancer it possesses new essential and non-apoptotic functions that are associated with regulating phospholipid synthesis including modulating mitochondrial phosphatidylserine decarboxylase activity. Here, we demonstrate additional functions for SMAC/Diablo associated with inflammation and immunity.

Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks.

Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility.

Synergistic interaction of N-3-Br-benzyl-noscapine and docetaxel abrogates oncogenic potential of breast cancer cells.

Noscapine, an opium alkaloid, was discovered to bind tubulin, arrest dividing cells at mitosis, and selectively induce apoptosis to cancer cells. N-3-Br-Benzyl-Noscapine (Br-Bn-Nos), one of the derivatives of noscapine, was demonstrated to have improved anticancer potential compared with noscapine. We approached to evaluate the single and combined effect of Br-Bn-Nos and docetaxel (DOX) based on molecular modeling and cellular study.

SMAC/Diablo controls proliferation of cancer cells by regulating phosphatidylethanolamine synthesis.

SMAC/Diablo, a pro-apoptotic protein, yet it is overexpressed in several cancer types. We have described a noncanonical function for SMAC/Diablo as a regulator of lipid synthesis during cancer cell proliferation and development. Here, we explore the molecular mechanism through which SMAC/Diablo regulates phospholipid synthesis.

Therapeutic strategies to overcome taxane resistance in cancer.

One of the primary causes of attenuated or loss of efficacy of cancer chemotherapy is the emergence of multidrug resistance (MDR). Numerous studies have been published regarding potential approaches to reverse resistance to taxanes, including paclitaxel (PTX) and docetaxel, which represent one of the most important classes of anticancer drugs. Since 1984, following the FDA approval of paclitaxel for the treatment of advanced ovarian carcinoma, taxanes have been extensively used as drugs that target tumor microtubules.

Toxicity of exhaust particulates and gaseous emissions from gasohol (ethanol blended gasoline)-fuelled spark ignition engines.

In the last couple of decades, blending of oxygenated additives with gasoline has been advocated to reduce dependence on fossil fuels and to reduce hazardous health effects of gaseous emissions and particulate matter (PM) emitted by internal combustion (IC) engines in the transport sector worldwide. The primary objective of this research was to carry out a comparative analysis of exhaust PM emitted by gasohol (gasoline blended with 10% ethanol, v/v)-fulled spark ignition (SI) engine with that of baseline gasoline-fuelled SI engine. To assess the PM toxicity, physical, chemical and biological characterizations of PM were carried out using the state-of-the-art instruments and techniques.

The VDAC1-based R-Tf-D-LP4 Peptide as a Potential Treatment for Diabetes Mellitus.

Diabetes mellitus is a metabolic disorder approaching epidemic proportions. Non-alcoholic fatty liver disease (NAFLD) regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. Recently, we demonstrated that the voltage-dependent anion channel 1 (VDAC1) is involved in NAFLD.

Potential role of arteether on N-methyl-D-aspartate (NMDA) receptor expression in experimental cerebral malaria mice and extension of their survival.

Cerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions.

Pyrrolidine-Acridine hybrid in Artemisinin-based combination: a pharmacodynamic study.

Aiming to develop new artemisinin-based combination therapy (ACT) for malaria, antimalarial effect of a new series of pyrrolidine-acridine hybrid in combination with artemisinin derivatives was investigated. Synthesis, antimalarial and cytotoxic evaluation of a series of hybrid of 2-(3-(substitutedbenzyl)pyrrolidin-1-yl)alkanamines and acridine were performed and mode of action of the lead compound was investigated. In vivo pharmacodynamic properties (parasite clearance time, parasite reduction ratio, dose and regimen determination) against multidrug resistant (MDR) rodent malaria parasite and toxicological parameters (median lethal dose, liver function test, kidney function test) were also investigated.

Ketoconazole, a cytochrome P(450) inhibitor can potentiate the antimalarial action of α/β arteether against MDR Plasmodium yoelii nigeriensis.

The emergence of multidrug resistant (MDR) strains of Plasmodium falciparum in South East Asia and other tropical countries, is posing serious challenge for the international efforts to eradicate malaria. New drug target/ACT/non-ACT combinations need to be discovered to control the spread of MDR malaria. The present communication deals with antimalarial potential of a new combination comprising of ketoconazole (KTZ) (an antifungal/inhibitor of CYP3A4) and artemisinin derivative α/β arteether (ART).

Antimalarial interaction of quinine and quinidine with clarithromycin.

Quinine (QN) and quinidine (QND) have been commonly used as effective and affordable antimalarials for over many years. Quinine primarily is used for severe malaria treatment. However, plasmodia resistance to these drugs and poor patient compliance limits their administration to the patients.