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Article: Cyclooxygenase and Lipoxygenase Gene Expression in the Inflammogenesis of Colorectal Cancer: Correlated Expression of EGFR, JAK STAT and Src Genes, and a Natural Antisense Transcript, RP11-C67.2.2.

Kennedy, Brian M / Harris, Randall E

2023 Volume 15, Issue 8

Abstract: We examined the expression of major inflammatory genes, cyclooxygenase-1, 2 (COX1, COX2), arachidonate-5-lipoxygenase (ALOX5), and arachidonate-5-lipoxygenase activating protein (ALOX5AP) among 469 tumor specimens of colorectal cancer in The Cancer ... ...

Abstract	We examined the expression of major inflammatory genes, cyclooxygenase-1, 2 (COX1, COX2), arachidonate-5-lipoxygenase (ALOX5), and arachidonate-5-lipoxygenase activating protein (ALOX5AP) among 469 tumor specimens of colorectal cancer in The Cancer Genome Atlas (TCGA). Among 411 specimens without mutations in mismatch repair (MMR) genes, the mean expression of each of the inflammatory genes ranked above the 80th percentile, and the overall mean cyclooxygenase expression (COX1+COX2) ranked in the upper 99th percentile of all genes. Similar levels were observed for 58 cases with MMR mutations. Pearson correlation coefficients exceeding r = 0.70 were observed between COX and LOX mRNA levels with genes of major cell-signaling pathways involved in tumorigenesis (Src, JAK STAT, MAPK, PI3K). We observed a novel association (r = 0.78) between ALOX5 expression and a natural antisense transcript (NAT), RP11-67C2.2, a long non-coding mRNA gene, 462 base pairs in length that is located within the terminal intron of the ALOX5 gene on chromosome 10q11.21. Tumor-promoting genes highly correlated with the expression of COX1, COX2, ALOX5 and ALOX5AP are known to increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the inflammogenesis of colorectal cancer. These genes and the novel NAT, RP1167C2.2 are potential molecular targets for chemoprevention and therapy of colorectal cancer.
Language	English
Publishing date	2023-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15082380
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Editorial: Mitochondria at the nexus of metabolism, aging, and disease.

Mallilankaraman, Karthik Babu / Kennedy, Brian K / Sorrentino, Vincenzo / Luciani, Alessandro

Frontiers in cell and developmental biology

2024 Volume 11, Page(s) 1356278

Language	English
Publishing date	2024-01-11
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1356278
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Article ; Online: The use of basic fibroblast growth factor to improve vocal function: A systematic review and meta-analysis.

Hamilton, Nick J I / Saccente-Kennedy, Brian / Ambler, Gareth

Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery

2023 Volume 48, Issue 5, Page(s) 725–733

Abstract: Objectives: This systematic review and meta-analysis examines if intralaryngeal injection of basic fibroblast growth factor 2 (FGF2) can improve voice outcomes in those with vocal disability.: Design: A Systematic review of original human studies ... ...

Abstract	Objectives: This systematic review and meta-analysis examines if intralaryngeal injection of basic fibroblast growth factor 2 (FGF2) can improve voice outcomes in those with vocal disability. Design: A Systematic review of original human studies reporting voice outcomes following intra-laryngeal injection of basic fibroblast growth factor 2 in those with vocal dysfunction. Databases searched were Medline (1946-July 2022), Embase (1947-July 2022), Cochrane database and Google Scholar. Setting: Secondary or tertiary care centres that undertook the management of voice pathology Hospital. Participants: Inclusion criteria were original human studies reporting voice outcome measurements following intralaryngeal injection of FGF2 to treat vocal fold atrophy, vocal fold scarring, vocal fold sulcus or vocal fold palsy. Articles not written in English, studies that did not include human subjects and studies where voice outcome measures were not recorded before and after FGF2 injection were excluded from the review. Main outcome measures: The primary outcome measure was maximum phonation time. Secondary outcome measures included acoustic analysis, glottic closure, mucosal wave formation, voice handicap index and GRBAS scale. Results: Fourteen articles were included out of a search of 1023 and one article was included from scanning reference lists. All studies had a single arm design without control groups. Conditions treated were vocal fold atrophy (n = 186), vocal cord paralysis (n = 74), vocal fold fibrosis (n = 74) and vocal fold sulcus (n = 56). A meta-analysis of six articles reporting on the use of FGF2 in patients with vocal fold atrophy showed a significant increase of mean maximum phonation time of 5.2 s (95% CI: 3.4-7.0) at 3-6 months following injection. A significant improvement in maximum phonation time, voice handicap index and glottic closure was found following injection in most studies assessed. No major adverse events were reported following injection. Conclusions: To date, intralaryngeal injection of basic FGF2 appears to be safe and it may be able to improve voice outcomes in those with vocal dysfunction, especially vocal fold atrophy. Randomised controlled trials are needed to further evaluate efficacy and support the wider use of this therapy.
MeSH term(s)	Humans ; Fibroblast Growth Factor 2/therapeutic use ; Plastic Surgery Procedures ; Vocal Cord Paralysis ; Laryngeal Diseases ; Atrophy
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2023-05-29
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	2205891-6
ISSN	1749-4486 ; 1749-4478 ; 0307-7772 ; 1365-2273
ISSN (online)	1749-4486
ISSN	1749-4478 ; 0307-7772 ; 1365-2273
DOI	10.1111/coa.14073
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Article ; Online: Investigating the biology of yeast aging by single-cell RNA-seq.

Zhang, Yi / Zhang, Xiannian / Kennedy, Brian K

Aging

2023 Volume 15, Issue 15, Page(s) 7340–7342

MeSH term(s)	Humans ; Saccharomyces cerevisiae/genetics ; Single-Cell Gene Expression Analysis ; Aging/genetics ; Biology ; Sequence Analysis, RNA ; Gene Expression Profiling
Language	English
Publishing date	2023-08-14
Publishing country	United States
Document type	Editorial
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204991
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Article ; Online: Hutchinson-Gilford Progeria paves the way for novel targeted anti-aging therapies.

Dreesen, Oliver / Kennedy, Brian

Med (New York, N.Y.)

2021 Volume 2, Issue 4, Page(s) 353–354

Abstract: Hutchinson-Gilford Progeria is an accelerated aging syndrome caused by permanently farnesylated mutant lamin A, termed progerin. Recently, the FDA approved Lonafarnib, a farnesyltransferase inhibitor, to treat progeria, while Koblan and colleagues used ... ...

Abstract	Hutchinson-Gilford Progeria is an accelerated aging syndrome caused by permanently farnesylated mutant lamin A, termed progerin. Recently, the FDA approved Lonafarnib, a farnesyltransferase inhibitor, to treat progeria, while Koblan and colleagues used novel gene editing methods to target the root cause of this disease by correcting the LMNA mutation.
MeSH term(s)	Aging ; Enzyme Inhibitors/therapeutic use ; Humans ; Lamin Type A/genetics ; Mutation ; Progeria/drug therapy
Chemical Substances	Enzyme Inhibitors ; Lamin Type A
Language	English
Publishing date	2021-04-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2021.03.005
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Article ; Online: A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence.

Pabis, Kamil / Barardo, Diogo / Sirbu, Olga / Selvarajoo, Kumar / Gruber, Jan / Kennedy, Brian K

eLife

2024 Volume 12

Abstract: Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and ... ...

Abstract	Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons. To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells, and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention, and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice. In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data suggest that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.
MeSH term(s)	Animals ; Mice ; Humans ; Aged ; Introns ; RNA-Seq ; Aging/genetics ; Promoter Regions, Genetic ; DNA Transposable Elements/genetics
Chemical Substances	DNA Transposable Elements
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.87811
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Article ; Online: A Systematic Review of Speech-Language Pathology Interventions for Presbyphonia Using the Rehabilitation Treatment Specification System.

Saccente-Kennedy, Brian / Gillies, Fiona / Desjardins, Maude / Van Stan, Jarrad / Govender, Roganie

Journal of voice : official journal of the Voice Foundation

2024

Abstract: Background: The prevalence of voice disorders for people aged >65 years is four times higher than for the population at large. The most common cause of dysphonia in this group is presbyphonia, the preferred first-line treatment for which is voice ... ...

Abstract	Background: The prevalence of voice disorders for people aged >65 years is four times higher than for the population at large. The most common cause of dysphonia in this group is presbyphonia, the preferred first-line treatment for which is voice therapy with a speech-language pathologist. This systematic review seeks to identify how voice therapy affects multidimensional voice outcomes in people with presbyphonia. Methods: A systematic search of CINAHL, Embase, Emcare, MEDLINE, and Google Scholar was conducted in March 2023. Comparative and noncomparative studies of voice therapy in participants aged >50 years with presbyphonia were considered for inclusion. No limitations were placed on date or language of publication. Study quality and risk of bias were assessed with the Cochrane Risk of Bias 2 tool and the Methodological Index for Non-Randomized Studies. Subgroup analysis was used to compare studies based on participant sex, intervention duration, study design, and intervention content. Interventions were specified using the Rehabilitation Treatment Specification System (RTSS) employing a consensus methodology among reviewers. The results were synthesized utilizing meta-analysis when outcomes were adequately specified and narrative analysis when they were not. Results: Twenty-three studies were included with 1050 subjects (mean age: 72.5 ± 8.6 years; 51% female). The most reported intervention was vocal function exercises. Per the RTSS, 14 interventions employed a predominantly Organ Functions approach, and the 14 remaining interventions employed a Skills & Habits approach. Meta-analysis confirmed posttherapy improvement in patient-related outcome measures of 0.93 standard mean difference (P < 0.00001, 95% confidence interval [CI]: 0.70-1.17); studies with predominantly males and with longer treatment periods were associated with larger improvements, while randomized controlled trials reported more modest improvements. Meta-analysis also identified a mean posttherapy increase in maximum phonation time (MPT) of 5.37 seconds (P < 0.00001, 95% CI: 3.52-7.22). Treatments with an Organ Functions focus resulted in greater gains in MPT than those with a Skills & Habits focus (7.52 seconds versus 2.90 seconds). Finally, meta-analysis identified reductions in acoustic perturbation measures (jitter: 0.62%, P < 0.001, 95% CI: 0.26%-0.97%; shimmer 1.05%, P < 0.00001, 95% CI: 0.67%-1.44%). Narrative synthesis further identified improvement in auditory-perceptual voice quality in all active treatment groups as well as improved glottal function in most studies that reported this. Conclusions: Despite the uncertainty around internal validity introduced by the inclusion of a wide range of study designs, there is convincing evidence that voice therapy for presbyphonia results in significant improvement in patient-reported, aerodynamic, acoustic, and expert-rated voice outcomes. Treatments with an Organ Functions focus may better address the underlying physiological deficits of presbyphonia, although future comparative studies with multidimensional voice assessment are warranted.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	17459-2
ISSN	1873-4588 ; 1557-8658 ; 0892-1997
ISSN (online)	1873-4588 ; 1557-8658
ISSN	0892-1997
DOI	10.1016/j.jvoice.2023.12.010
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Article ; Online: Novel method of breaking down barriers in the provision of menopause care in Ireland.

Kennedy, Brian / Lundy, Deirdre / Mackey, Rachel / Hartley, Caoimhe / Soffe, Karen

Post reproductive health

2023 Volume 29, Issue 3, Page(s) 143–147

Abstract: Aim: A novel method of providing education and support to GP's was developed. The goal was to create a rapidly accessed peer advisory community to empower GP HRT prescribing.: Method: A core group of doctors with special expertise in HRT were ... ...

Abstract	Aim: A novel method of providing education and support to GP's was developed. The goal was to create a rapidly accessed peer advisory community to empower GP HRT prescribing. Method: A core group of doctors with special expertise in HRT were assembled on a GP interest group on the Telegram messaging platform. It is called 'HRT prescribers', an educational community with entrance by peer invitation. Most are GPs and number between 800 and 1000. Members post clinical questions and receive evidence-based responses to their dilemmas. Results: A survey of members was overwhelmingly positive. 98% agreed the group empowered them to be confident and feel supported in their HRT prescribing. 90% agreed the group helped improve access to HRT for women who needed it in their practice. Conclusion: This project developed, with the cooperation of specialists, a cost-effective rapid method of educating and empowering GP's to be supported to safely treat their patients in their menopause transition. With further support and development, we believe it is the model that could be adopted in many countries.
MeSH term(s)	Humans ; Female ; Ireland ; Menopause ; Emotions
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2753537-X
ISSN	2053-3705 ; 2053-3691
ISSN (online)	2053-3705
ISSN	2053-3691
DOI	10.1177/20533691231198946
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Article ; Online: Aging inverts the effects of p75

Wang, Zijun / Kennedy, Brian K / Wong, Lik-Wei / Sajikumar, Sreedharan

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Volume 37, Issue 8, Page(s) e23067

Abstract: Age-induced impairments in learning and memory are in part caused by changes to hippocampal synaptic plasticity during aging. The p75 neurotrophin receptor ( ... ...

Abstract	Age-induced impairments in learning and memory are in part caused by changes to hippocampal synaptic plasticity during aging. The p75 neurotrophin receptor (p75
MeSH term(s)	Animals ; Male ; Mice ; Aging ; Hippocampus/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Neuronal Plasticity ; Neurons/metabolism ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Ngfr protein, mouse
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202201640RRR
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Zs.MO 296: Show issues

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Article ; Online: A Comparison of the Effects of Phonation into a Positive Expiratory Pressure Device and Silicone Tube in Water on the Vocal Mechanism.

Amarante Andrade, Pedro / Frič, Marek / Saccente-Kennedy, Brian / Hruška, Viktor

Journal of voice : official journal of the Voice Foundation

2023

Abstract: Objectives: Positive expiratory pressure (PEP) devices have become an additional therapeutic approach for treating voice disorders. Similar to water resistance therapy (WRT), phonation in a PEP device introduces a secondary source of vibration within ... ...

Abstract	Objectives: Positive expiratory pressure (PEP) devices have become an additional therapeutic approach for treating voice disorders. Similar to water resistance therapy (WRT), phonation in a PEP device introduces a secondary source of vibration within the vocal tract. This investigation aimed to compare the effects of phonation using a PEP device and silicone tube phonation (STP) commonly used in WRT on the vocal mechanism during phonation. Methods: Three normophonic subjects participated in the study. High-speed videoendoscopy, pressure, airflow, electroglottography, and acoustic recordings were collected. Results: The results demonstrated that phonation using both the PEP device and silicone tube induced alterations in glottal behavior. The PEP device produced more pronounced and consistent pressure oscillations, impacting the glottal cycle and influencing parameters including contact quotient (CQ), fundamental frequency, glottal area, pressure, and airflow. The regular vibratory mechanism of the PEP device systematically modified the glottal cycle. In STP, regular bubbling at lower depths of submersion produced higher CQ values, supporting the efficacy of deep bubbling exercises for inducing glottal adduction. Conclusions: The findings suggest that phonation using PEP devices has a more pronounced impact on the vocal tract and glottis. It also provides a stronger massage effect that directly affects the glottal source. Phonation with a silicone tube produces similar results, although to a lesser extent and with lower regularity. These findings offer guidance in the selection of voice therapy devices.
Language	English
Publishing date	2023-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	17459-2
ISSN	1873-4588 ; 1557-8658 ; 0892-1997
ISSN (online)	1873-4588 ; 1557-8658
ISSN	0892-1997
DOI	10.1016/j.jvoice.2023.10.022
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