Comment on Salazar et al. Weight Regain after Metabolic Surgery: Beyond the Surgical Failure. J. Clin. Med. 2024, 13, 1143.

I read the article by Salazar J. [...].

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC) Treatment: Quo Vadis?

Lung cancer has been established as the second most common cancer worldwide (most common cancer in men and second most common cancer in women) and as the leading cause of cancer morbidity among neoplasms [...].

Effect of Spirulina Nigrita® Supplementation on Indices of Exercise-Induced Muscle Damage after Eccentric Protocol of Upper Limbs in Apparently Healthy Volunteers.

Spirulina is a supplement with antioxidant and anti-inflammatory properties that may enhance performance and recovery after intense exercise. The present study aimed to investigate the effects of Spirulina Nigrita® on physical performance, and recovery markers after intense eccentric exercise in healthy moderately physically active volunteers. In a double-blind crossover design, participants were supplemented either with spirulina (42 mg Kg-1 BW per day) or a placebo for 15 days before conducting an eccentric exercise protocol using the non-dominant arm. A six-week washout period was required between conditions. Performance and mobility markers such as isometric peak torque (PTQ), ligament range of motion (ROM), and perceived muscle discomfort (VAS) were assessed and blood samples (CK, LDH) were obtained at 1, 24, 48, and 72 h post-exercise. No significant differences were noticed between the two conditions on any of the investigated markers, indicating that spirulina supplementation has no positive effect on isometric muscle performance or alleviation of exercise-induced muscle damage (EIMD) symptoms in the specific population.

Hypocalcemia in the Immediate Postoperative Period Following Metabolic Bariatric Surgery - Hype or Harm?

PURPOSE: Hypocalcemia post-metabolic bariatric surgery (MBS) is a known long-term complication after hypoabsorptive procedures. However, data on immediate postoperative calcium are limited. Our aim was to evaluate the prevalence of hypocalcemia on the 1st postoperative day after MBS and correlate it with potential associated factors. MATERIALS AND METHODS: We analyzed data from all consecutive index MBS over 1 year. We collected data on demographics and on preoperative and postoperative values of serum calcium (TC), albumin, adjusted calcium (AC-Payne formula), magnesium, phosphorus, preoperative vitamin-D, and postoperative 24-h urine output, intravenous fluids (IVF), bolus intravenous furosemide, and creatine phosphokinase (CPK). Continuous data are expressed as means ± SD (range). Categorical data are presented as frequencies (%). Linear regression was implemented to designate potential correlations. RESULTS: The cohort included 86 patients (58.1% females). The mean preoperative TC was 9.4mg/dL ± 0.4 (8.5-10.5) and mean postoperative TC 7.8mg/dL ± 0.6 (6.3-9.3, 17.0% decrease). The mean preoperative AC was 10.1mg/dL ± 0.4 (9.2-11.2) and mean postoperative AC 8.5mg/dL ± 0.6 (7.0-10.0, 15.8% decrease). Seventy-three patients (84.8%) had abnormally low TC (< 8.5mg/dL), and 43 (50%) abnormally low AC. There was only weak correlation between postoperative TC and AC with magnesium (r = 0.258), phosphorus (r = 0.269), vitamin-D (-0.163), 24-h urine output (r = -0.168), IVF (r = -0.237), bolus furosemide (r = 0.155), and mean operative time (r = 0.010). CONCLUSIONS: In our cohort of patients, hypocalcemia was a real problem but we did not find any significant correlation with the examined factors. Further studies are warranted to validate our findings and investigate other potential correlations.

Hungry for fat: Metabolic crosstalk with lipid-rich CAFs fuels pancreatic cancer.

Some cancers prefer to metabolize lipids for their growth and metastasis. In a recent Cancer Cell study, Niu et al. revealed that SET domain containing 2, histone lysine methyltransferase (SETD2)-deficient pancreatic cancer cells induce the differentiation of lipid-laden cancer-associated fibroblasts (CAFs), which, in turn, transport lipids to promote tumor growth.

RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.

Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and less in v-RAF murine sarcoma viral oncogene homolog B (BRAF) and mitogen-activated protein-kinase kinase (MEK), all key components of the RTK-RAS-mitogen-activated protein kinase (MAPK) pathway. Learning from melanoma, the identification of BRAFV600E substitution in NSCLC provided the rationale for the investigation of RAF and MEK inhibition as a therapeutic strategy. The regulatory approval of two RAF-MEK inhibitor combinations, dabrafenib-trametinib, in 2017, and encorafenib-binimetinib, in 2023, signifies a breakthrough for the management of BRAFV600E-mutant NSCLC patients. However, the almost universal emergence of acquired resistance limits their clinical benefit. New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.

Anthocyanins in Non-Small Cell Lung Cancer (NSCLC) Treatment and Prevention.

An ever-growing volume of data supports the important role of dietary interventions in cancer prevention and the beneficial effects of plant secondary metabolites in solid tumor therapeutics [...].

Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities.

Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development and progression of bone loss disorders, but also in the bone-specific aspect of other clinical entities, such as the tumorigenesis of solid organs. Novel treatment options have come into sight that exploit the mechanosensitivity of osteoblasts, osteocytes, and chondrocytes to achieve efficient bone regeneration. In this regard, runt-related transcription factor 2 (Runx2) has emerged as a chief skeletal-specific molecule of differentiation, which is prominent to induction by mechanical stimuli. Polycystins represent a family of mechanosensitive proteins that interact with Runx2 in mechano-induced signaling cascades and foster the regulation of alternative effectors of mechanotransuction. In the present narrative review, we employed a PubMed search to extract the literature concerning Runx2, polycystins, and their association from 2000 to March 2024. The keywords stated below were used for the article search. We discuss recent advances regarding the implication of Runx2 and polycystins in bone remodeling and regeneration and elaborate on the targeting strategies that may potentially be applied for the treatment of patients with bone loss diseases.

Up to the Herculean Task of Tackling Cancer Therapy Resistance.

Cancer therapy resistance still poses the biggest hurdle to cancer treatment [...].

Malolactone strikes: K-Ras-G12D's Achilles' heel.

In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.

Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients-mostly autologous from a single Unit-along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated-p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

The ras-related protein RAB22A interacts with hypoxia-inducible factor 1-alpha (HIF-1α) in MDA-MB-231 breast cancer cells in hypoxia.

BACKGROUND: Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) and the small GTPase protein Ras-related protein Rab-22 A (RAB22A) may be colocalized in the cytoplasm and that as a conequence they may enhance the formation of microvesicles in breast cancer cells under hypoxia. Therefore, we sought to determine whether these two proteins are present in intracellular complexes in breast carcinoma cells. METHODS AND RESULTS: Evaluation using molecular docking indicated that HIF-1α and RAB22A interact with each other. Co-immunoprecipitation of endogenous or ectopically expressed HIF-1α and RAB22A proteins in MDA-MB-231 breast cancer cells or HEK-293T cells demonstrated that endogenous HIF-1α and RAB22A can form an intracellular complex; however, transiently expressed HIF-1α and RAB22A failed to interact. Investigating RAB22A and HIF-1α interactions in various cancer cell lines under hypoxia may shed light on their roles in cancer cell survival and progression through regulation of intracellular trafficking by HIF-1α under hypoxic conditions. CONCLUSIONS: Our study is the first to reveal the potential involvement of HIF-1α in intracellular trafficking through physical interactions with the small GTPase protein RAB22A. We discuss the implications of our work on the role of exosomes and microvesicles in tumor invasiveness.

Mechanotransduction Circuits in Human Pathobiology.

It is widely acknowledged that mechanical forces exerted throughout the human body are critical for cellular and tissue homeostasis [...].