The SIRT7-nucleolus connection in cancer: ARF enters the fray.

The nucleolar enzyme sirtuin 7 (SIRT7) promotes cancer progression in certain malignancies, likely in part by controlling ribosome biosynthesis. Recently, we discovered that SIRT7 destabilizes the cyclin dependent kinase inhibitor 2A (CDKN2A, known as ARF) within the nucleolus, aiding cancer progression. We propose that targeting nucleolar SIRT7 offers promise for new anti-cancer therapies.

Benzene: A critical review on measurement methodology, certified reference material, exposure limits with its impact on human health and mitigation strategies.

Benzene is a carcinogenic pollutant with significant emission sources present in the atmosphere. The need for accurate and precise measurement of benzene in the atmosphere has become increasingly evident due to its toxicity and the adverse health effects associated with exposure to different concentrations. Certified reference material (CRM) is essential to establish the traceability of measurement results. The present review compiles the available national and international measurement methods, certified reference materials (CRMs) for benzene and the limit of benzene in fuel composition (v/v) worldwide. Overall, the review indicates the benzene level in the atmosphere and the resulting impacts on the environment and human health, which frequently exceed the exposure limits of different environment regulatory agencies. An extensive literature review was conducted to gather information on monitoring and analysis methods for benzene, revealing that the most preferred method, i.e. Gas Chromatography- Flame Ionization Detector and Mass Spectrometry, is neither cost-effective nor suitable for real-time continuous monitoring. By analysing existing literature and studies, this review will shed light on the understanding of the importance of benzene pollution monitoring in ambient air and its implications for public health. Additionally, it will reflect the mitigation strategies applied by regulators & need for future revisions of air quality guidelines.

Identification of Small Molecule Inhibitors Targeting Phosphoserine Phosphatase: A Novel Target for the Development of Antiamoebic Drugs.

Amoebiasis, a widespread disease caused by the protozoan parasite Entamoeba histolytica, poses challenges due to the adverse effects of existing antiamoebic drugs and rising drug resistance. Novel targeted drugs are in need of the hour to combat the prevalence of this disease. Given the significance of cysteine for Entamoeba survival, the rate-determining step in the serine (the sole substrate of cysteine synthesis) biosynthetic pathway, i.e., the conversion of 3-phosphoserine to l-serine catalyzed by phosphoserine phosphatase (PSP), emerges as a promising drug target. Our previous study unveils the essential role of EhPSP in amoebas' survival, particularly under oxidative stress, by increasing cysteine production. The study also revealed that EhPSP differs significantly from its human counterpart, both structurally and biochemically, highlighting its potential as a viable target for developing new antiamoebic drugs. In the present study, employing in silico screening of vast natural and synthetic small chemical compound libraries, we identified 21 potential EhPSP inhibitor molecules. Out of the 21 compounds examined, only five could inhibit the catalytic activity of EhPSP. The inhibition capability of these five compounds was subsequently validated by in silico binding free energy calculations, SPR-based real-time binding studies, and molecular simulations to assess the stability of the EhPSP-inhibitor complexes. By identifying the five potential inhibitors that can target cysteine synthesis via EhPSP, our findings establish EhPSP as a drug candidate that can serve as a foundation for antiamoebic drug research.

SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF.

Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.

Pyrazole Paradigms: Unveiling Synthetic Pathways and Unraveling Anti-Cancer Potential.

This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to change the pyrazole core structure, resulting in new compounds with improved pharmacological properties. The paper also covers the mechanisms of action that underpin pyrazole derivatives' anti-cancer characteristics, focusing on interactions with major molecular targets implicated in cancer growth and proliferation. SAR insights help to rationally develop novel anti-cancer drugs. In conclusion, the review emphasizes the versatility of pyrazole derivatives as scaffolds for the discovery and development of new anti-cancer medicines. By understanding synthesis routes and unravelling anti-cancer potential, this study hopes to encourage new research endeavours focused on leveraging the therapeutic advantages of pyrazole paradigms in the fight against cancer.

SIRT7: a novel molecular target for personalized cancer treatment?

The Sirtuin family of NAD+-dependent enzymes assumes a pivotal role in orchestrating adaptive responses to environmental fluctuations and stress stimuli, operating at both genomic and metabolic levels. Within this family, SIRT7 emerges as a versatile player in tumorigenesis, displaying both pro-tumorigenic and tumor-suppressive functions in a context-dependent manner. While other sirtuins, such as SIRT1 and SIRT6, exhibit a similar dual role in cancer, SIRT7 stands out due to distinctive attributes that sharply distinguish it from other family members. Among these are a unique key role in regulation of nucleolar functions, a close functional relationship with RNA metabolism and processing -exceptional among sirtuins- and a complex multienzymatic nature, which provides a diverse range of molecular targets. This review offers a comprehensive overview of the current understanding of the role of SIRT7 in various malignancies, placing particular emphasis on the intricate molecular mechanisms employed by SIRT7 to either stimulate or counteract tumorigenesis. Additionally, it delves into the unique features of SIRT7, discussing their potential and specific implications in tumor initiation and progression, underscoring the promising avenue of targeting SIRT7 for the development of innovative anti-cancer therapies.

Modified Thoracolumbar Interfascial Plane Block Versus Erector Spinae Plane Block in Patients Undergoing Spine Surgeries: A Randomized Controlled Trial.

BACKGROUND: Lumbar spine surgery is associated with significant postoperative pain. Interfascial plane blocks, such as erector spinae plane (ESP) and thoracolumbar interfascial plane (TLIP) blocks, can play a significant role in multimodal analgesic regimens. METHODS: Sixty patients aged 18 to 60 years undergoing elective single or double-level lumbar discectomy or primary lumbar laminoplasty were recruited into this randomized double­blind study. All patients received general anesthesia and were randomly allocated to either modified TLIP (mTLIP) block (group M) or ESP block (group E). Postoperative and intraoperative fentanyl consumption, and postoperative pain scores, were recorded. RESULTS: Total 48 h postoperative fentanyl consumption was higher in Group M (189.66±141.11 µg) than in Group E (124.16±80.83 µg; P =0.031). In the first 24 postoperative hours, fentanyl consumption was higher in Group M (150.3±120.9 µg) than in group E (89.9±65.3 µg; P =0.01) but was similar between groups in postoperative hours 24to 48 (39.0±20.2 µg versus 34.7±17.1 µg in group M and group E, respectively; P =0.37). Additional intraoperative fentanyl requirement was 57.66±21.76 µg in group M compared with 40.33±21.89 µg in group E ( P <0.01). Postoperative pain scores were higher in group M than in group E at 1, 2, 4, 6, 12, and 24 hours postoperatively ( P <0.001), but similar at 48 hours ( P =0.164). CONCLUSION: Compared with the mTLIP block, the ESP block was associated with lower pain scores and a small decrease in perioperative fentanyl consumption in patients undergoing lumbar spine surgeries. Both blocks could form a part of a multimodal analgesic regimen in spine surgery patients.

Wild Edible Flowers of Western Himalayas: Nutritional Characterization, UHPLC-QTOF-IMS-Based Phytochemical Profiling, Antioxidant Properties, and In Vitro Bioaccessibility of Polyphenols.

Four edible flowers commonly consumed in the Western Himalayan region, namely, Bauhinia variegata (Kachnar), Tropaeolum majus (Nasturtium), Matricaria chamomilla (Chamomile), and Tagetes erecta (Marigold), were characterized for their nutritional and phytochemical composition. Through the UHPLC-QTOF-IMS-based metabolomics approach, 131 compounds were tentatively identified consisting of phenolic acids, flavonoid glycosides, terpenoids, amino acids, and fatty acid derivatives. Kaempferol and quercetin glycosides for Kachnar, apigenin glycosides and caffeoylquinic acid derivatives for Chamomile, patulin and quercetin derivatives for Marigold, cyanidin and delphinidin glycosides for Nasturtium were the predicted marker metabolites identified through non-targeted metabolomics. Kachnar and Chamomile scored best in terms of macronutrients and essential micronutrients, respectively. Nasturtium contained high concentrations of α-linolenic acid, anthocyanins, and lutein. Kachnar contained the highest total phenolic acids (63.36 ± 0.38 mg GAE g-1), while Marigold contained the highest total flavonoids (118.90 ± 1.30 mg QUE g-1). Marigolds possessed excellent free radical scavenging and metal chelation activities. Chamomile exhibited strong α-glucosidase inhibition activity, followed by Nasturtium. The in vitro gastrointestinal digestibility of flower extracts indicated that the bioaccessibility of phenolic acids was higher than that of flavonoids. Polyphenols from Nasturtium and Chamomile showed the highest bioaccessibility. The study is an attempt to characterize traditionally consumed edible flowers and promote their wider utilization in gastronomy and nutraceuticals.

Seasonal and diurnal measurement of ambient benzene at a high traffic inflation site in Delhi: Health risk assessment and its possible role in ozone formation pathways.

Benzene is the most toxic and hazardous pollutant among volatile organic compounds (VOCs), as it comes under group 1 carcinogens recognized by the International Agency for Research on Cancer (IARC). It also plays a significant role in forming secondary pollutants like ozone. The benzene concentration was measured using a charcoal sorbent tube by active sampling at a traffic junction and analysis was done using GC-FID. The maximum average concentration of benzene in ambient air was found to be 33 µg/m3. A diurnal study of benzene measurement shows higher benzene concentrations in the evening compared to the morning. Seasonal variation of benzene is found to be winter > spring > summer > autumn > monsoon and OFP was found to be 21, 19, 14, 13, and 10 respectively. Cancer (ILCR) and non-cancer (HQ) health risk assessment was done to determine the impact of ambient benzene on the residents of urban areas. The yearly average value of ILCR was found to be 2×10-6 ± 1×10-6 which ranges from acceptable value to three times the WHO acceptable value i.e 1×10-6. The correlation of ozone and its precursor, benzene with meteorological parameters is also evaluated. The correlation of benzene and ozone with solar radiation shows the influence of photochemical reactions on the levels of benzene and ozone at the study site, although it is low.

Comparison of the efficacy of pericapsular nerve group block (PENG) block versus suprainguinal fascia iliaca block (SFIB) in total hip arthroplasty: A randomized control trial.

Background and Aims: Hip replacement surgery is a commonly performed surgery with the aim of improving mobility in patients suffering from hip conditions. Though the modified suprainguinal approach of fascia iliaca block (SFIB) is commonly used, the analgesic efficacy is moderate and is associated with quadriceps weakness. The pericapsular nerve group (PENG) block has been used to block the sensory articular branches of the hip joint in various hip surgeries. This study aimed to compare SFIB with PENG block in terms of pain relief, opioid consumption and their adverse effects in patients undergoing primary total hip arthroplasties. (THA). Methods: Seventy ASA I/II patients undergoing primary THA were enrolled in this double-blinded, randomized trial. Patients were randomly allocated to one of the two groups: Group P: ultrasound (US)-guided PENG block and Group S: patients received the US-guided SFIB. Results: Postoperatively, there was statistically significant difference in numerical rating scale (NRS) scores at all-time intervals. Total morphine consumption in 24 hours and 48 hours was statistically more in SFIB group. Five patients had quadriceps weakness in the SFIB group. There was no difference in any other adverse effects. Conclusion: US-guided PENG block significantly reduces perioperative morphine consumption and pain scores in THA patients when compared to SFI block. It is not associated with quadriceps weakness as seen in SFIB.

Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.

Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2 g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.

Anti-cancer peptides: their current trends in the development of peptide-based therapy and anti-tumor drugs.

Human cancer remains a cause of high mortality throughout the world. The conventional methods and therapies currently employed for treatment are followed by moderate-to-severe side effects. They have not generated curative results due to the ineffectiveness of treatments. Besides, the associated high costs, technical requirements, and cytotoxicity further characterize their limitations. Due to relatively higher presidencies, bioactive peptides with anti-cancer attributes have recently become treatment choices within the therapeutic arsenal. The peptides act as potential anti-cancer agents explicitly targeting tumor cells while being less toxic to normal cells. The anti-cancer peptides are isolated from various natural sources, exhibit high selectivity and high penetration efficiency, and could be quickly restructured. The therapeutic benefits of compatible anti-cancer peptides have contributed to the significant expansion of cancer treatment; albeit, the mechanisms by which bioactive peptides inhibit the proliferation of tumor cells remain unclear. This review will provide a framework for assessing anti-cancer peptides' structural and functional aspects. It shall provide appropriate information on their mode of action to support and strengthen efforts to improve cancer prevention. The article will mention the therapeutic health benefits of anti-cancer peptides. Their importance in clinical studies is elaborated for reducing cancer incidences and developing sustainable treatment models.

Efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus undergoing coronary artery bypass graft surgery: A non-inferiority randomized trial.

AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.

Perioperative role of oral gabapentin as an analgesic in paediatric patients: A randomised controlled trial.

Background and Aims: Surgical procedure commonly performed in the advanced pediatric age group includes urogenital surgery, adenotonsillectomy, etc., Aim: The aim of this study is to determine the effect of single-dose gabapentin 15 mg/kg on acute pain in the immediate postoperative period in patients aged 8-14 years undergoing surgeries under general anesthesia. Material and Methods: After the approval from the institutional ethical committee, 60 American Society of Anesthesiologists (ASA) I and II patients aged 8-14 years undergoing urogenital surgeries (orchidopexy/urethroplasty) under general anesthesia were included in this study. The patients were assigned into one of the two treatment groups. Patients in group I received oral gabapentin 15 mg/kg dissolved in 5 mL of honey 2 h before surgery, while patients in group II received 5 mL honey orally 2 h before surgery. Results: A total of 60 patients participated. Patients in group I had lower consumption of fentanyl perioperatively (intraoperatively: 1.36 ± 0.70 mcg/kg; postoperatively: 2.36 ± 0.795 mcg/kg) than group II (intraoperatively: 1.8 ± 0.6 mcg/kg; postoperatively: 2.9 ± 0.47 mcg/kg). The differences in the two groups were significant. The time to first rescue analgesia was greater in group I (3.03 ± 0.60 h) than in group II (2.26 ± 0.57 h). There was an increase in sedation score in the treatment group. Conclusion: Our clinical study demonstrates that a 15 mg/kg single preemptive oral dose of gabapentin might reduce the requirement of analgesics perioperatively in pediatric urogenital surgery but might also be associated with undesirable effects such as increased sedation.

SIRT7 and p53 interaction in embryonic development and tumorigenesis.

p53 is a hallmark tumor suppressor due in part to its role in cell cycle progression, DNA damage repair, and cellular apoptosis; its protein activity interrelates with the Sirtuin family of proteins, major regulators of the cellular response to metabolic, oxidative, and genotoxic stress. In the recent years, mammalian Sirtuin 7 (SIRT7) has emerged as a pivotal regulator of p53, fine-tuning its activity in a context dependent manner. SIRT7 is frequently overexpressed in human cancer, yet its precise role in tumorigenesis and whether it involves p53 regulation is insufficiently understood. Depletion of SIRT7 in mice results in impaired embryo development and premature aging. While p53 activity has been suggested to contribute to tissue specific dysfunction in adult Sirt7 -/- mice, whether this also applies during development is currently unknown. By generating SIRT7 and p53 double-knockout mice, here we show that the demise of SIRT7-deficient embryos is not the result of p53 activity. Notably, although SIRT7 is commonly considered an oncogene, SIRT7 haploinsufficiency increases tumorigenesis in p53 knockout mice. Remarkably, in specific human tumors harboring p53 mutation, we identified that SIRT7 low expression correlates with poor patient prognosis. Transcriptomic analysis unveils a previously unrecognized interplay between SIRT7 and p53 in epithelial-to-mesenchymal transition (EMT) and extracellular matrix regulation with major implications for our understanding of embryonic development and tumor progression.

Edible rose flowers: A doorway to gastronomic and nutraceutical research.

The world is moving towards a healthier lifestyle where people are changing their eating habits, which influenced edible rose flowers to emerge as a pioneer in the field of nutraceutical and food industries. Roses are a good source of dietary phytochemicals viz., flavonoids (anthocyanins, flavonols, and flavonols), carotenoids, and phenolic acids. The presence of such phytochemicals makes rose as an anti-oxidant, anti-inflammatory, anti-cancerous, anti-aging, anti-microbial, hepatoprotective, and neurogenic agent. Historically edible rose flowers have been used in the preparation of traditional food products and delicacies such as gulkand, punkhuri, and rose petal tea and have found application in traditional medicine such as Ayurveda to treat hyperacidity, vata, pitta, constipation, abdominal pains, and various other illnesses. Over a period of time, concept of edible flowers has gotten more recognition and now roses are used in the preparation of many food products such as jams, jellies, cookies, salads, ice-creams, juices, and wines. In this review, we established a connection between phytochemicals and their biological activity, nutritional composition, traditional usage, and functional food aspects of edible rose flowers. Overall, these concepts help to set a new trend in culinary science and further research on the nutraceutical composition, and health benefits of edible rose flowers.

Carbon Dots Conjugated Antibody as an Effective FRET-Based Biosensor for Progesterone Hormone Screening.

In this work, carbon dots (CDs) were synthesized by a one-step hydrothermal method using citric acid and ethylene diamine, and covalently functionalized with antibodies for the sensing of progesterone hormone. The structural and morphological analysis reveals that the synthesized CDs are of average size (diameter 8-10 nm) and the surface functionalities are confirmed by XPS, XRD and FT-IR. Further graphene oxide (GO) is used as a quencher due to the fluorescence resonance energy transfer (FRET) mechanism, whereas the presence of the analyte progesterone turns on the fluorescence because of displacement of GO from the surface of CDs effectively inhibiting FRET efficiency due to the increased distance between donor and acceptor moieties. The linear curve is obtained with different progesterone concentrations with 13.8 nM detection limits (R2 = 0.974). The proposed optical method demonstrated high selectivity performance in the presence of structurally resembling interfering compounds. The PL intensity increased linearly with the increased progesterone concentration range (10-900 nM) under the optimal experimental parameters. The developed level-free immunosensor has emerged as a potential platform for simplified progesterone analysis due to the high selectivity performance and good recovery in different samples of spiked water.