Most cited article: Recent PARP Inhibitor Advancements in Cancer Therapy: A Review

Author(s): Pulla Prudvi Raj, Kaviarasan Lakshmanan, Gowramma Byran*, Kalirajan Rajagopal, Praveen Thaggikuppe Krishnamurthy and Divya Jyothi Palati

Abstract:

Poly [ADP-ribose] polymerase-1 [PARP-1] is a chromatin-bound nuclear enzyme that gets activated by DNA damage. It facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Increased PARP-1 expression is observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. PARP-1 interacts directly and indirectly with various oncogenic proteins and regulates several transcription factors, thereby modulating carcinogenesis. There is a lot of pre-clinical and clinical data supporting the use of PARP-1 inhibitors [PARP-1i] in cancers that express homologous recombination deficiencies like mutations within the BRCA-1/2 genes. Therapeutic inhibition of PARP-1 is therefore perceived as a promising anticancer strategy, and numerous PARP-1i are currently under development and clinical evaluation. Currently, there are 4 FDA-approved PARP-1i products on the market, and a few more are in the last stage of clinical development. All the molecules are non-selective PARP-1i. While giving promising results, PARP-1i has its own disadvantages, like safety problems, resistance, etc. Looking at the success rate of PARP-1i in various solid tumors, there is a need for novel and selective PARP-1i. In this review, we discuss various aspects related to PARP-1i, like recent developments, overcoming resistance, and selectivity criteria of new molecules for potential PARP-1i.

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Animated abstract: Dietary Technologies to Optimize Healing from Injury-Induced Inflammation

Author(s):Barry Sears*, Mary Perry and Asish K. Saha*

Abstract

Inflammation is an acute adaptive response to injury. However, if the initial inflammatory response to an injury is not completely healed, it becomes chronic low-level inflammation that is strongly associated with many chronic disease states, including metabolic (obesity and diabetes), cardiovascular, auto-immune, and neurogenerative disorders as well as cancer. The healing process is far more complex than the initiation of inflammation. Within that complexity of healing is a sequence of events that are under profound dietary control and can be defined by specific blood markers. Those molecular events of the healing process that are under significant dietary control are termed as the Resolution Response. The purpose of this review is to describe the molecular components of the Resolution Response and how different dietary factors can either optimize or inhibit their actions. In particular, those dietary components that optimize the Resolution Response include a calorie-restricted, protein-adequate, moderate-carbohydrate, low-fat diet referred to as the Zone diet, omega-3 fatty acids, and polyphenols. The appropriate combination of these dietary interventions constitutes the foundation of Pro-Resolution Nutrition. The effect of these dietary components the actions of NF-κB, AMPK, eicosanoids, and resolvins are described in this review, as well as ranges of appropriate blood markers that indicate success in optimizing the Resolution Response by dietary interventions.

Read the article here: http://bit.ly/3Jk7Phb

Podcast: Innovative Ingredients Fortified Nutrients Enriched Biscuits and Cookies: Quality and Sensory Analyses

Author(s):Niladri Chakraborty* and Rajat Chakraborty

Abstract:

Global suffering from COVID-19 has necessitated augmenting the immunity systems of humans through the consumption of macro-micro-nutrients and antioxidant-enriched fortified foods. In this article, fortifications of popular bakery products, viz. biscuits, and cookies, have been reviewed, encompassing the novel fortifying ingredients and innovative methods employed with an emphasis on the overall enrichment of the final product quality. A few notable features concerning novel fortified biscuits and fortified cookies have been decisively summarized. Wheat flour blended with 40% sesame-cake flour resulted in a fortified biscuit possessing higher protein (16.6%), crude fat (16.95%), and dietary fiber (8.2%) with acceptable sensory characteristics. About 9% toting up of chicken eggshell dried powder could result in high Ca content in biscuits with customary changes in texture and sensory properties. A remarkable 5% addition of bee pollen to wheat flour appreciably improved the nutrient compositions (carbohydrate 65.18%, protein 7.32%, and total dietary fiber 1.47%) along with high polyphenol and antioxidant potentials. Notably, mixing fish fillet protein concentrate with wheat flour could yield enhanced nutritional content (protein 14.63-19.52%, fat 16.2-16.5%), as well as augmented amino acids. Remarkably, wheat flour fortified with fermented jack bean flour resulted in an overall fortified biscuit with substantial carbohydrates, crude protein, fat, fiber, ash, and appreciable macro-micro mineral contents and sensory characteristics. Innovative fortified cookies were made by blending wheat flour or Brewer’s spent grain flour with one or more ingredients, e.g. full-fat soya, mushroom, cardamom powder, moringa leaves, coconut, sweet potato flour rendering amplified values of nutrients, superior physical properties, increased mineral and flavonoid contents and organoleptic qualities.

Read the full article here: http://bit.ly/3Rkqewn

Podcast: Amino acids profile in children with acute brucellosis

Author(s): Ahmet Guzelcicek, Nihayet Bayraktar and Mehmet Bayraktar*

Background: Many new cases of brucella infections are seen in Turkey every year, especially in March, April, and May, due to the consumption of local unpasteurized cheese. Amino acids profiles have not been studied in brucellosis so far.

Aims: The amino acid profiles may be affected by infectious diseases. Our study aims to evaluate the plasma amino acid profile in the progression of acute brucellosis. Methods: Plasma amino acid profile was performed by an 8045 LC-MS / MS device (Shimadzu 8045, Japan) using JASEM amino acid kit.

Results: Analysis of 45 amino acid profiles was made and results profiles showed significant differences in concentrations and types of amino acids in brucella patients. We observed a significant difference in terms of alanine, arginine, aspartic acid, glutamine, glutamic acid, glycine, isoleucine, ornithine, phenylalanine, proline, tyrosine, valine, alpha-aminoadipic acid, alpha-amino-pimelic acid, argininosuccinic acid, gamma-aminobutyric acid, this proline, 1-methylhistidine, 3-methylhistidine, hydroxylysine, hydroxyproline, cystine, serotonin, ethanolamine, and taurine (p-value < 0.05 for each). No significant differences were determined regarding asparagine, citrulline, histidine, leucine, alloisoleucine, lysine, methionine, serine, threonine, tryptophan, anserine, alpha aminobutyric acid, beta aminoisobutyric acid, beta-alanine, cystathionine, histamine, and 5-oh-trp (p-value > 0.05 for all).

Conclusion: Patients with brucellosis have a specific profile of amino acids which may reflect sequelae of pathological and metabolic biochemical changes in the disease process due to the growth of Brucella spp. in the human body leading to an imbalance of amino acid levels.

Read the Article here: http://bit.ly/3XL2WCv

Podcast: Research and Patents Status of Selected Phytochemicals Against Cancer: How Close and How Far?

Author(s):Homa Fatma and Hifzur R Siddique*

Background: Cancer is a global health issue and economic burden with a continuous increase in incidence and mortality. Over the years, the underlying molecular mechanism of cancers was thoroughly researched, leading to multiple drugs development. Unfortunately, most drugs have some serious drawbacks, such as therapy resistance and toxicity. Epidemiological studies have shown that a diet rich in fruits and vegetables has cancer-prevention properties, which shifted the attention to the potential role of phytochemicals in anti-carcinogenic activity.

Objective: To review the present status of phytochemicals research and patents in cancer prevention and chemosensitization.

Methods: We explored the relevant published articles and patents to review the phytochemicals showing cancer preventive role in preclinical settings from 1997 onwards.

Results: We summarise the role of phytochemicals on anti-carcinogenic, anti-inflammatory, antiproliferative, anti-metastatic, and pro-apoptotic activities in both in vitro and in vivo. Thus, phytochemicals might be an excellent chemosensitizing agent against chemoresistant cells and possibly one of the safest and most effective options for cancer therapy. However, one of the limitations of phytochemicals is their poor bioavailability and rapid excretion. Several analogs have been introduced to increase bioavailability, better biological efficacy, absorption, and retention. In fact, various phytochemicals and their analogs have been patented for their anti-cancerous properties.

Conclusion: This mini-review discusses various phytochemicals and their anti-cancerous and chemosensitizing roles. Due to their clinical relevance, recent trends in phytochemical extraction and exploration have shown that more and more phytochemicals are being patented.

Read the full article here: https://bit.ly/3wC5jeT

Current article: Recent Updates on Oral and Dermal Film-based Formulations and their Applications

Author(s): Saily Shinde, Mihir Ghonge, and Harsha Kathpalia*

Abstract:

On the one hand, oral formulations are susceptible to problems, including instability accompanied by erratic absorption throughout the gastrointestinal tract, first-pass metabolism, and patient-related and pathological difficulties in consumption. On the other hand, the world has been observing a shift from conventional dermal formulations to more cosmetically attractive ones. Amid all these, polymeric films and film-forming systems have emerged as promising candidates for addressing the above problems. Oral films have been studied for their potential applications in immediate and sustained-release formulations and have markedly shown increased plasma concentrations of drugs that otherwise undergo degradation in the gastrointestinal tract and the liver and have an obvious edge in treating pathologies of the oral cavity. At the same time, a variety of dermal film formulations have been developed and studied for treating wounds, skin infections and pathologies, corns and calluses, and managing pain. This review article attempts to cover significant findings in oral and dermal applications of these formulations under one umbrella and provide readers with a compilation of relevant research works and marketed formulations.

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Current article: Highlighting the Potential Role of Exosomes as the Targeted Nanotherapeutic Carrier in Metastatic Breast Cancer

Author(s): Alisha Khera, Hema K. Alajangi, Akhil Khajuria, Ravi P. Barnwal*, Santosh Kumar* and Gurpal Singh*

Abstract:

Breast cancer, being the second most common type of cancer, is a leading cause of death in the female population. Of all the available treatments existing for breast cancer, exosomes appear as an important medium for the site targeted delivery of drugs. Exosomes, unlike all the other extracellular vesicles, play a vital role in the transport of numerous biomolecules throughout the body and can easily be detected because of the presence of specific biomarkers. Apart from playing a wide variety of roles in the progression of many diseases, they are also responsible for tumor progression and metastasis in breast cancer. Exosomes and related engineering strategies are being discussed as nano-carrier for the delivery of different drugs in the case of breast cancer. Overall, we have discussed in this review the role of exosomes in breast cancer and the engineering strategies being devised for making them an efficient drug delivery system.

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Podcast: Basic Guidelines for Bacteriophage Isolation and Characterization

Author(s): Safia Samir*

Abstract:

The world is on the cusp of a post-antibiotic period. A century ago, before the advent of antibiotics, bacteriophage therapy was the treatment of choice for bacterial infections. Although bacteriophages have yet to be approved as a treatment in Western medicine, researchers and clinicians have begun to anticipate phage therapy. Bacteriophages are viruses that depend on bacterial cell metabolism to multiply. They offer a promising alternative to the use of antibiotics and an excellent antibacterial option for combating multidrug resistance in bacteria. However, not every phage is suitable for phage therapy. In particular, prophages should not be used because they can lysogenize host cells instead of lysing them. To offer adequate therapeutic options for patients suffering from various infectious diseases, a wide selection of different phages is needed. While there is no evidence of direct toxicity induced by phage particles, it is crucial to study mammalian cell–phage interactions. This requires phage preparations to be free of bacterial cells, toxins and other compounds to avoid skewing host responses. Negative staining of purified viruses and electron microscopy remain the gold standard in the identification of bacteriophages. Interestingly, genomics has greatly changed our understanding of phage biology. Bacteriophage genome sequencing is essential to obtain a complete understanding of the bacteriophages’ biology and to obtain confirmation of their lifestyle. Full genetic sequencing of bacteriophage will enable a better understanding of the phage-encoded proteins and biomolecules (especially phage lytic enzymes) involved in the process of bacterial cell lysis and death. Mass spectrometry can be used for the identification of phage structural proteins. The use of lytic phages as biocontrol agents requires the most appropriate and standard methods to ensure application safety. This review pursues recent research and methods in molecular biology for the isolation and characterization of phages to facilitate follow-up and implementation of work for other researchers. Patents related to this topic have been mentioned in the text.

Journal link: http://bit.ly/3GraUct

Podcast: http://bit.ly/3k2E0qY

Podcast: Contribution of Pharmaceutical Care to Person-centered Health Care and the Safety of Pharmacotherapy for Hospitalized Older Individuals in Brazil: An Investigative Single-arm Intervention Trial

Author(s): Alan Maicon de Oliveira*, Fabiana Rossi Varallo, João Paulo Vilela Rodrigues, Guilherme José Aguilar, Nereida Kilza da Costa Lima and Leonardo Régis Leira Pereira

Background: Adverse drug events (ADE) and medication errors (ME) provide large numbers of victims. Older people are more susceptible to these events, due to the continuing search for several chronic degenerative disease treatments. The Third Global Patient Safety Challenge announced the objective of reducing unnecessary polypharmacy, encouraging deprescription, and aiming to ensure the prescription of medications in an appropriate manner, based on the best evidence and taking into account the individual factors of people.

Objective: To evaluate whether Pharmaceutical Care (PC), when inserted in a geriatric ward and the context of person-centered health care, cooperates with the safety of pharmacotherapy in older individuals in Brazil.

Methods: This is an investigative, single-arm, preliminary study. Inclusion criteria: individuals aged ≥60 years and admitted to the geriatric ward between August 2019 to January 2020. The PC (with the practice of pharmacotherapeutic follow-up, medication reconciliation, and pharmacotherapy review) was made available to identify ADE and ME, as well as the associated factors and clinical outcomes, were analyzed.

Results: 60 participants were included. It was found that, on hospital admission, 93.3% of them were polymedicated and 86.7% had a history of using potentially inappropriate medications (PIM). ADE and ME were detected in 43 individuals (71.7%) and, in total, 115 incidents were identified, with drugs that act on the nervous system associated with them (31.9%). Acceptance of the PC’s recommendations reached the rate of 85.2%. Polypharmacy (p=0.03) and the presence of multiple diseases (p=0.03) had an effect on the presentation of ADE and ME. The number of medications in use decreased in the comparison between admission and hospital discharge (p<0.0001).

Conclusion: This investigative study indicated that ADE and ME are linked to the polypharmacy in use at the beginning of hospitalization. On the other hand, we showed that the PC (inserted in the multidisciplinary team) contributed to the deprescribing of medications at hospital discharge. Therefore, the PC can provide improvements in this scenario.

Trial Registration: Brazilian Registry of Clinical Trials (registration number: RBR-34f2px4).

Watch the podcast here: http://bit.ly/3GfRuXH
Read the full article: http://bit.ly/3VRB51K

Editor’s choice: Synthesis of Hexahydroxy Strontium Stannate/Tin Dioxide Nanocomposites and their Photocatalytic Properties for Gentian Violet

Author(s):Chunhu Yu, Zeyang Xue, Yajing Mao, Jianfeng Huang, Feihu Tao, Zhengyu Cai, Chuangang Fan and Lizhai Pei*

Background: Gentian violet dye released from industries into the environment has caused serious water pollution and is a significant environmental pollutant to human beings owing to the toxicity. It is urgent to decrease environmental pollution by removing gentian violet in the wastewater.

Objective: The aim is to synthesize hexahydroxy strontium stannate/tin dioxide nanocomposites by a simple hydrothermal method without surfactants and research the photocatalytic performance for gentian violet degradation.

Methods: Hexahydroxy strontium stannate/tin dioxide nanocomposites have been obtained via the hydrothermal method. The structure, size, morphology and photocatalytic performance were characterized by X-ray diffraction, electron microscopy, solid ultraviolet-visible diffuse reflectance spectroscopy and X-ray photoelectron spectroscopy.

Results: The nanocomposites possess oven-shaped morphology with the size of less than 100 nm and are composed of hexagonal SrSn(OH)₆ and tetragonal SnO₂ phases. The band gap of the nanocomposites is 3.52 eV. 10 mg hexahydroxy strontium stannate/tin dioxide nanocomposites have the ability to completely degrade 10 mL gentian violet solution with the concentration of 10 mgL^-1 under 6 h ultraviolet-visible light irradiation. Hydroxyl radical, hole and superoxide radical are the main species for the gentian violet photocatalytic degradation using the nanocomposites.

Conclusion: The hexahydroxy strontium stannate/tin dioxide nanocomposites show good photocatalytic performance for the GV degradation. The photocatalytic performance for gentian violet degradation using the hexahydroxy strontium stannate/tin dioxide nanocomposites depends on the irradiation time and content of the nanocomposites.

Read more: https://bit.ly/3hFj7Bi