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Aim: To demonstrate the prognostic importance of glucose-to-lymphocyte ratio (GLR) and uric acid (UA) in patients with metastatic breast cancer (MBC) receiving Cdk 4/6 inhibitors. Materials & methods: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, GLR, UA and CA15-3 were analyzed to assess their prognostic value using Kaplan–Meier curves and Cox regression analysis in 101 patients with MBC, retrospectively. Results: Importantly, both progression-free survival and overall survival were shorter in the group with high neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), GLR and UA. In the multivariate analysis, GLR and UA levels were independent prognostic factors for both progression-free survival and overall survival. Conclusion: In patients with MBC, GLR and UA are independent factors that predict survival times.

Background: It is well known that oncologic management of elderly patients is complicated, and physicians should well define the ultimate goals when choosing treatment modalities. Cancer treatment should not necessarily focus on survival but aim for a good quality of life for the patient in light of their frailty. Patients and Methods: This is a retrospective cross-sectional survey study. One hundred fifty-eight women with breast cancer participated in this study. The PRISMA-7 Frailty Index and WHOQOL-OLD Module assessed participants’ frailty and quality of life. SPSS 26.0 and Medcalc 14 [Acacialaan 22, B-8400 Ostend, Belgium] programs were used for statistical analyses. Statistically significant associations between the PRISMA-7 scale and the WHOQOL-OLD Module were assessed. Results: Of the158 participants, the median age [min-max] was 71 [65-96] years, and 61.2% had stage I and II breast cancer. Lumpectomy was 61.1%, and 75% received chemotherapy-radiotherapy and hormone therapy. For the WHOQOL-OLD domains; financial status [p=0.001] with the sensory ability domain, work status [p

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease characterized by the TGF-β (transforming growth factor-β)–dependent differentiation of lung fibroblasts into myofibroblasts, which leads to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by myofibroblasts requires de novo synthesis of glycine, the most abundant amino acid found in collagen protein. TGF-β upregulates the expression of the enzymes of the de novo serine–glycine synthesis pathway in lung fibroblasts; however, the transcriptional and signaling regulators of this pathway remain incompletely understood. Here, we demonstrate that TGF-β promotes accumulation of ATF4 (activating transcription factor 4), which is required for increased expression of the serine–glycine synthesis pathway enzymes in response to TGF-β. We found that induction of the integrated stress response (ISR) contributes to TGF-β–induced ATF4 activity; however, the primary driver of ATF4 downstream of TGF-β is activation of mTORC1 (mTOR Complex 1). TGF-β activates the PI3K-Akt-mTOR pathway, and inhibition of PI3K prevents activation of downstream signaling and induction of ATF4. Using a panel of mTOR inhibitors, we found that ATF4 activation is dependent on mTORC1, independent of mTORC2. Rapamycin, which incompletely and allosterically inhibits mTORC1, had no effect on TGF-β–mediated induction of ATF4; however, Rapalink-1, which specifically targets the kinase domain of mTORC1, completely inhibited ATF4 induction and metabolic reprogramming downstream of TGF-β. Our results provide insight into the mechanisms of metabolic reprogramming in myofibroblasts and clarify contradictory published findings on the role of mTOR inhibition in myofibroblast differentiation.

Sanitary products (SPs) such as toilet paper and moist wipes are marketed as flushable products (FPs). SP manufacturers, wastewater authorities, and governmental agencies describe FPs in their own terms, and cause confusion about what is safe to flush with respect to sewer operations. To identify sewer-safe FPs, 11 toilet paper (TP) and 39 flushable wipe (FW) samples that were collected from around the world were examined to assess critical links between their fiber compositions, strength indicators, and disintegration performance. The findings illustrate that products that are made of primarily wood-pulp fibers have low strength, disintegrate rapidly, and are safe flushables. In contrast, products that contain strong and synthetic fibers (e.g. polyester) exhibit high strength, disintegrate slowly, and pose significant risk of accumulation in sewer systems. Suggestions are offered for product improvement and for long-term sustainability of FPs and wastewater infrastructures.

Individuals with Alzheimer's disease and other neurodegenerative diseases have been exposed to excess risk by the COVID-19 pandemic. COVID-19's main manifestations include high body temperature, dry cough, and exhaustion. Nevertheless, some affected individuals may have an atypical presentation at diagnosis but suffer neurological signs and symptoms as the first disease manifestation. These findings collectively show the neurotropic nature of SARS-CoV-2 virus and its ability to involve the central nervous system. In addition, Alzheimer's disease and COVID-19 has a number of common risk factors and comorbid conditions including age, sex, hypertension, diabetes, and the expression of APOE ε4. Until now, a plethora of studies have examined the COVID-19 disease but only a few studies has yet examined the relationship of COVID-19 and Alzheimer's disease as risk factors of each other. This review emphasizes the recently published evidence on the role of the genes of early- or late-onset Alzheimer's disease in the susceptibility of individuals currently suffering or recovered from COVID-19 to Alzheimer's disease or in the susceptibility of individuals at risk of or with Alzheimer's disease to COVID-19 or increased COVID-19 severity and mortality. Furthermore, the present review also draws attention to other uninvestigated early- and late-onset Alzheimer's disease genes to elucidate the relationship between this multifactorial disease and COVID-19.

Background: Oxidative stress is a significant feature in the pathomechanism of neurodegenerative diseases. Thus, the search for an effective and safe novel antioxidant agent with neuroprotective properties has increased the interest in medicinal plant products as a bioactive phytochemical source. However, little is known about the potential effects of the medically important Glaucium corniculatum as a natural antioxidant. Objective: In the present study, it was aimed to investigate the anti-oxidative, anti-apoptotic, and cell cycle regulatory mechanisms underlying the neuroprotective effects of alkaloid extracts (chloroform, methanol, and water) from G. corniculatum, which was profiled for major alkaloid/alkaloids, against H2O2-induced neuronal damage in differentiated PC12 cells. Materials and methods: The profiles of the alkaloid extracts were analyzed by GC-MS. The effects of the alkaloid extracts on intracellular ROS production, level of apoptotic cells, and cell cycle dysregulation were analyzed by flow cytometry; the effects on mRNA expression of apoptosis-related genes were also analyzed by qRT-PCR. Results: The same alkaloid components, allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide were obtained in all three solvents, but the ratios of the components differed according to the solvents. Allocryptopine was determined to be the major alkaloid ingredient in the alkaloid extracts, with the highest amount of allocryptopine (497 mu g/mg) being found in the chloroform alkaloid extract (CAE) (*p < 0.05). The best results were obtained from CAE, which has the highest amount of allocryptopine among alkaloid extracts in all studies. CAE suppressed intracellular ROS production (5.7-fold), percentage of apoptotic cells (3.0-fold), and cells in the sub G1 phase (6.8-fold); additionally, it increased cells in the G1 phase (1.5-fold) (**p < 0.01). CAE remarkably reduced the expressions of Bax, Caspase-9/-3 mRNA (2.4-3.5-fold) while increasing the expression of Bcl-2 mRNA (3.0-fold) (*p < 0.05). Conclusions: Our results demonstrated that alkaloid extracts from G. corniculatum, which contain allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide suppressed oxidative stress-induced neuronal apoptosis, possibly by suppressing the mitochondrial apoptotic pathway and regulating the cell cycle. These results are the first report that related alkaloids have played a neuroprotective role by regulating multiple mechanisms. Thus, our study indicated that these alkaloids especially allocryptopine could offer an efficient and novel strategy to explore novel drugs for neuroprotection and cognitive improvement.

Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with significant morbidity and mortality. Because currently available therapies have limited effect, there is a need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that transforming growth factor (TGF)-β, a key cytokine that promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate-limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-β. In this study, we investigated whether inhibition of de novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that TGF-β induces mRNA and protein expression of PHGDH in murine fibroblasts. Similarly, intratracheal administration of bleomycin resulted in increased expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly developed small molecule inhibitor of PHGDH (NCT-503), we tested whether pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-β–induced collagen protein synthesis. Mice treated with the PHGDH inhibitor beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis. These results indicate that the de novo serine and glycine synthesis pathway is necessary for TGF-β–induced collagen synthesis and bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo serine and glycine synthesis pathway may be a therapeutic target for treatment of fibrotic diseases, including idiopathic pulmonary fibrosis.

Background: Several studies indicate that chemokines play important roles in colorectal mucosal immunity. The chemokine CXCL5 which is expressed by epithelial cells within colorectal mucosa is a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer. The purpose of this study was to investigate whether serum and tissue CXCL5 levels is altered in colorectal carcinomas (CRC) compared to colonic adenoma and normal mucosa.It also aimed to compare colon adenoma and colorectal cancer for blood CXCL5 and CEA levels, their sensitivity, and specificity. Methods: CXCL5 expression was assessed with immunohistochemistry staining in biopsy samples taken during colonoscopy in 22 colonic adenomas, 23 colorectal carcinomas and 23 normal colonic tissue samples. Also all patients’ serum CXCL5 and CEA levels were measured. This stduy was prospective observational study. Results: The number of cases who were stained positive with immunohistochemistry was found to be higher in the group with CRC. When compared with the other groups, both levels of serum CXCL5 and CEA were significantly high in the group CRC. Sensitivity and specificity of serum CXCL5 were found to be low as a result of the ROC analysis. Conclusion: Although the level of CXCL5 is high in CRC, its level in serum is not significant enough to support the early diagnosis of the disease.