Site-selective protein-modification chemistry for basic biology and drug development.

Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.We thank FCT Portugal (FCT Investigator to G.J.L.B.), the EU (Marie-Curie CIG to G.J.L.B. and Marie-Curie IEF to O.B.) and the EPSRC for funding. G.J.L.B. is a Royal Society University Research Fellow.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.239

Dietary Inflammatory Index and Head and Neck Cancer: A Multicenter Case-Control Study in Iran

Background: The inflammatory potential of diet may affect carcinogenesis. This study aimed to determine the association between dietary inflammatory index (DII) and the risk of head and neck cancer (HNC), as well as the interaction between DII and cigarette smoking in HNC development within the Iranian population. Study Design: This is a case-control study. Methods: In this multicenter case-control study, participants’ dietary intake was assessed using a validated 130-item food frequency questionnaire, from which DII was computed. The study recruited 876 new cases from referral hospitals across 10 provinces and 3409 healthy controls who were frequency-matched based on age, gender, and residential place. Logistic regression was used to obtain odds ratios (ORs) for HNC across tertiles of DII, which were adjusted for confounding variables. Results: A higher pro-inflammatory diet was associated with an increased risk of all HNC (OR T3 vs. T1 [95% CI]: 1.31 [1.06, 1.62]; P-trend = 0.013). There was a significant association between lip and oral cavity cancers and DII (OR T3 vs. T1 [95% CI]: 1.56 [1.16, 1.66]; P-trend = 0.004). Furthermore, an inflammatory diet was associated with an increased risk of pharynx cancer (OR T3 vs. T1 [95% CI]: 2.08 [1.14, 3.79]; P-trend = 0.02). Additionally, no significant association was observed between DII and larynx cancer, while an interaction was found between DII and tobacco use on the risk of HNC (OR T3 vs. T1 [95% CI]: 2.52 [1.78, 3.57]; P-interaction = 0.03). Conclusion: DII was positively associated with HNC risk. There was a significant association between DII and the risk of lip, oral cavity, and pharynx cancers. Additionally, there was an interaction between tobacco use and DII in determining the risk of HNC

The Iranian Study of Opium and Cancer (IROPICAN): Rationale, design, and initial findings

Background: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. Methods: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. Results: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. Conclusion: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum

Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran

Background: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. Methods: We used the IROPICAN database in Iran and employed multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. Results: We analyzed 717 cases and 3477 controls and a subset of 215 patients and 2145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 (95% CI: 0.69, 1.20), we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR=1.78, 95% CI 1.16, 2.72) compared to non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR=2.25, 95% CI: 1.21, 4.18) and for initiating waterpipe smoking at an age less than 20 (OR=2.73, 95% CI 1.11, 6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR=2.35, 95% CI 1.24-4.42) than in current smokers (OR=1.52, 95% CI 0.72-3.15). All observed associations were consistently higher for urothelial histology. Conclusions: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. Impact: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers

Graduate entry to medicine in Iran

<p>Abstract</p> <p>Backgrounds</p> <p>In Iran medical students are selected from high school graduates via a very competitive national university entrance exam. New proposals have been seriously considered for admitting students from those with bachelor degrees. We assessed the opinions of different stakeholders on the current situation of admission into medicine in Iran, and their views on positive and negative aspects of admitting graduates into medicine.</p> <p>Methods</p> <p>We conducted five focus group discussions and seven in-depth interviews with stakeholders including medical students, science students, university professors of basic sciences, medical education experts, and policy makers. Main themes were identified from the data and analyzed using content analysis approach.</p> <p>Results</p> <p>Medical students believed "graduate admission" may lead to a more informed choice of medicine. They thought it could result in admission of students with lower levels of academic aptitude. The science students were in favor of "graduate admission". The education experts and the professors of basic science all mentioned the shortcomings of the current system of admission and considered "graduate admission" as an appropriate opportunity for correcting some of the shortcomings. The policy makers pointed out the potential positive influences of "graduate admission" on strengthening basic science research. They thought, however, that "graduate admission" may result in lengthening the overall duration of medical education, which is already long in Iran (over 7 years). On the whole, the participants thought that "graduate admission" is a step in the right direction for improving quality of medical education.</p> <p>Conclusion</p> <p>"Graduate admission" has the potential to correct some of shortcomings of medical education. Unlike other countries where "graduate admission" is used mainly to admit students who are mentally mature, in Iran the main objective seems to be strengthening basic sciences.</p

COP27 Climate Change Conference: urgent action needed for Africa and the world

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COP27 climate change conference: Urgent action needed for Africa and the world

No Abstract

COP27 Climate Change Conference: urgent action needed for Africa and the world

No abstract