Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.
Background: There is limited research on how patients prefer physicians to communicate about the topic of obesity, and there is even less understanding of which terms physicians most commonly use.Methods: In this cross-sectional, nonrandom sampling study, patients who were seeking treatment for weight loss rated the desirability of 12 terms to describe excess weight, and physicians rated the likelihood with which they would use those terms during clinical encounters. Participants rated terms on a 5-point scale, with ؊2 representing "very undesirable" or "definitely would not use" and ؉2 representing "very desirable" or "definitely would use."Results: Patients (n ؍ 143; mean age, 46.8 years; mean body mass index, 36.9 kg/m 2 ) rated "weight" (mean ؎ SD) as the most desirable term (1.13 ؎ 1.10), although it did not significantly differ from 5 other terms provided. They rated "fatness" (؊1.30 ؎ 1.22) as the most undesirable term, although this rating did not differ significantly from 4 other terms. Physicians affiliated with a community-based medical school (n ؍ 108; mean age, 48.8 years; 79.6% primary care specialty) were most likely to use "weight" (1.42 ؎ 0.89), which was significantly different from ratings for all other terms. They were least likely to use "fatness" (؊1.74 ؎ 0.59), although this rating did not differ significantly from 3 other terms.Conclusion: Physicians generally reported that they use terminology that patients had rated more favorably, and they tend to avoid terms that patients may find undesirable. Understanding the preferences and terminology used by patients and physicians is an important initial step to ensure that communications related to obesity and weight loss are efficient and effective. The provision of weight loss counseling by physicians in primary care settings offers a potentially effective approach to combating the problem of overweight and obesity.1-4 However, physicians often neglect broaching the topics of obesity and weight loss during primary care encounters. 3,[5][6][7][8] Barriers that may hinder physicians' provision of weight-loss counseling include time constraints, lack of reimbursement, and perceptions that treatment will be ineffective. In addition, physicians may feel ill-equipped to address these issues. 5,9 -12 Despite these barriers, overweight and obese patients may desire greater involvement of their primary care physician in weight-loss counseling and treatment efforts. 6,7 Until recently, however, few studies have examined how patients would prefer their physicians to discuss the topic of obesity. In one study, obese patients rated the term "weight" as significantly more desirable than a variety of terms physicians could use to describe excess weight; they rated "obesity," "excess fat," and "fatness" as the most undesirable terms physicians could use. 13 The parents of pediatric patients overwhelmingly preferred that physicians use the phrase "gaining too much weight" as compared with other options, including "overweight," when discussing their chi...
Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-β1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.
Results supported a mediation effect, such that the treatment effect on physical activity was completely mediated by changes in self-efficacy. Although replication is needed, results support the theoretical rationale for targeting self-efficacy to promote physical activity among patients with type 2 diabetes.
Laparoscopic surgery is an acceptable alternative to open surgery in colorectal cancer treatment. However, in gastric cancer, there is not much scientific evidence. Here, we proposed a prospective randomized clinical trial to evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. From October 2010 to September 2012, 300 patients with gastric cancer were randomized to undergo either laparoscopy-assisted gastrectomy (LAG) or conventional open gastrectomy (OG) with D2 dissection. Clinicopathological parameters, recovery and complications were compared between these two groups. Thirty cases were excluded because of refusing to be involved in the trial, having peritoneal seeding metastasis or LAG conversed to OG, and finally 270 cases were analyzed (128 in LAG and 142 in OG). No significant differences were observed in gender, age, body mass index, stages and types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)] (P > 0.05). The number of harvested lymph nodes (HLNs) was similar (29.3 ± 11.8 in LAG vs. 30.1 ± 11.4 in OG, P = 0.574). And in the same type of radical resection, no significant difference was found in the number of HLNs between the two groups (PG + D2, P = 0.770; DG + D2, P = 0.500; TG + D2, P = 0.993). The morbidity of the LAG group (21.8 %) was also comparable to the OG group (19.0 %, P = 0.560). However, the LAG group had significantly less blood loss and faster recovery, and a longer operation time (P < 0.05). Laparoscopic D2 dissection is feasible, safe and capable of fulfilling oncologic criteria for the treatment of gastric cancer.
Recruitment of the GTPase dynamin-related protein 1 (Drp1) to mitochondria is a central step required for mitochondrial fission. Reversible Drp1 phosphorylation has been implicated in the regulation of this process, but whether Drp1 phosphorylation at Ser-637 determines its subcellular localization and fission activity remains to be fully elucidated. Here, using HEK 293T cells and immunofluorescence, immunoblotting, RNAi, subcellular fractionation, co-immunoprecipitation assays, and CRISPR/Cas9 genome editing, we show that Drp1 phosphorylated at Ser-637 (Drp1pS637) resides both in the cytosol and on mitochondria. We found that the receptors mitochondrial fission factor (Mff) and mitochondrial elongation factor 1/2 (MIEF1/2) interact with and recruit Drp1pS637 to mitochondria and that elevated Mff or MIEF levels promote Drp1pS637 accumulation on mitochondria. We also noted that protein kinase A (PKA), which mediates phosphorylation of Drp1 on Ser-637, is partially present on mitochondria and interacts with both MIEFs and Mff. PKA knockdown did not affect the Drp1-Mff interaction, but slightly enhanced the interaction between Drp1 and MIEFs. In Drp1-deficient HEK 293T cells, both phosphomimetic Drp1-S637D and phospho-deficient Drp1-S637A variants, like wild-type Drp1, located to the cytosol and to mitochondria and rescued a Drp1 deficiency-induced mitochondrial hyperfusion phenotype. However, Drp1-S637D was less efficient than Drp1-WT and Drp1-S637A in inducing mitochondrial fission. In conclusion, the Ser-637 phosphorylation status in Drp1 is not a determinant that controls Drp1 recruitment to mitochondria.
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