وَنُوحًا إِذۡ نَادَىٰ مِن قَبۡلُ فَٱسۡتَجَبۡنَا لَهُۥ فَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ
Long before that, We answered Noah when he cried out to Us: We saved him and his family from the great calamity
How stress registers in the body over time.
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وَنُوحًا إِذۡ نَادَىٰ مِن قَبۡلُ فَٱسۡتَجَبۡنَا لَهُۥ فَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ
Long before that, We answered Noah when he cried out to Us: We saved him and his family from the great calamity
وَنَجَّيۡنَٰهُمَا وَقَوۡمَهُمَا مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ
We saved them and their people from great distress
وَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ
We saved him and his people from great distress
قُلِ ٱللَّهُ يُنَجِّيكُم مِّنۡهَا وَمِن كُلِّ كَرۡبࣲ ثُمَّ أَنتُمۡ تُشۡرِكُونَ
Say, ‘God rescues you from this and every distress; yet still you worship others beside Him.’
وَلَمَّا بَلَغَ أَشُدَّهُۥٓ ءَاتَيۡنَٰهُ حُكۡمࣰ ا وَعِلۡمࣰ اۚ وَكَذَٰلِكَ نَجۡزِي ٱلۡمُحۡسِنِينَ
When he reached maturity, We gave him judgement and knowledge: this is how We reward those who do good
وَلَا تَقۡرَبُواْ مَالَ ٱلۡيَتِيمِ إِلَّا بِٱلَّتِي هِيَ أَحۡسَنُ حَتَّىٰ يَبۡلُغَ أَشُدَّهُۥۚ وَأَوۡفُواْ ٱلۡكَيۡلَ وَٱلۡمِيزَانَ بِٱلۡقِسۡطِۖ لَا نُكَلِّفُ نَفۡسًا إِلَّا وُسۡعَهَاۖ وَإِذَا قُلۡتُمۡ فَٱعۡدِلُواْ وَلَوۡ كَانَ ذَا قُرۡبَىٰۖ وَبِعَهۡدِ ٱللَّهِ أَوۡفُواْۚ ذَٰلِكُمۡ وَصَّىٰكُم بِهِۦ لَعَلَّكُمۡ تَذَكَّرُونَ
Stay well away from the property of orphans, except with the best [intentions], until they come of age; give full measure and weight, according to justice’- We do not burden any soul with more than it can bear- ‘ when you speak, be just, even if it concerns a relative; keep any promises you make in God’s name. This is what He commands you to do, so that you may take heed’
Commentary on the verses above, at most two editions per verse.
And mention Noah what follows Nūhan substitutes for it when he called when he supplicated to God against his people — with the words My Lord do not leave upon the earth any inhabitant from among the disbelievers … to the end of the verse Q. 7126 before that is before the time of Abraham and Lot. And We responded to him and delivered him and his people who were in the Ark with him from the great agony namely from drowning and his people’s denial of him.
and We delivered them and their people the Children of Israel from the great distress namely Pharaoh’s enslavement of them.
And We delivered him and his family from the great distress which was the drowning
And (remember) Nuh, when he cried (to Us) aforetime. We answered to his invocation and saved him and his family from the great distress (76)We helped him against the people who denied Our Ayat. Verily, they were a people given to evil. So We drowned them all (77) Nuh and His People Allah tells us how He responded to His servant and Messenger Nuh, peace be upon him, when he prayed to Him against his people for their disbelief in him: فَدَعَا رَبَّهُ أَنِّي مَغْلُوبٌ فَانتَصِرْ (Then he invoked his Lord (saying): "I have been overcome, so help (me)!")(54:10) وَقَالَ نُوحٌ رَّبِّ لَا تَذَرْ عَلَى الْأَرْضِ مِنَ الْكَافِرِينَ دَيَّارًا - إِنَّكَ إِن تَذَرْهُمْ يُضِلُّوا عِبَادَكَ وَلَا يَلِدُوا إِلَّا فَاجِرًا كَفَّارًا (And Nuh said: "My Lord! Leave not any inhabitant of the disbelievers on the earth! If You leave them, they will mislead Your servants, and they will beget none but wic
And, indeed We gave Our grace to Musa and Harun (114)And We saved them and their people from the great distress (115)And helped them, so that they became the victors (116)And We gave them the clear Scripture (117)And guided them to the right path (118)And We left for them among the later generations (119)"Salam (peace!) be upon Musa and Harun! (120)Verily, thus do We reward the doers of good (121)Verily, they were two of Our believing servants (122) Musa and Harun Allah tells us how He blessed Musa and Harun with prophethood and how He saved them, along with those who believed, from the oppression of Fir'awn and his people, who had persecuted them by killing their sons and sparing their women, and by forcing them to do the most menial tasks, then ultimately He caused them to prevail over them and to seize their lands and their wealth and all that they had spent their entire lives amass
And indeed Nuh invoked Us, and We are the best of those who answer (75)And We rescued him and his family from the great distress (76)And, his progeny, them We made the survivors (77)And left for him (a goodly remembrance) among the later generation (78)"Salam (peace!) be upon Nuh among the all creatures! (79)Verily, thus We reward the gooddoers (80)Verily, he [Nuh] was one of Our believing servants (81)Then We drowned the others (82) Nuh and His People When Allah tells us about how most of the early people went astray from the path of salvation, He starts the detailed explanation of that with the story of Nuh and the rejection of his people. Only a few of Nuh's people believed in him, despite the long period of time he spent among them. He stayed among them for one thousand years less fifty, and after he stayed among them for so long and their disbelief became too much for him to bear
Sound narrations only, and never matched by text. A narration appears here because a compiler filed it under a chapter this subject maps to, or because someone read it and anchored it. Each row says which.
حَدَّثَنِي عَبْدُ اللَّهِ بْنُ مُحَمَّدٍ، حَدَّثَنَا عَبْدُ الْمَلِكِ بْنُ عَمْرٍو، حَدَّثَنَا زُهَيْرُ بْنُ مُحَمَّدٍ، عَنْ مُحَمَّدِ بْنِ عَمْرِو بْنِ حَلْحَلَةَ، عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي سَعِيدٍ الْخُدْرِيِّ، وَعَنْ أَبِي هُرَيْرَةَ، عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ " مَا يُصِيبُ الْمُسْلِمَ مِنْ نَصَبٍ وَلاَ وَصَبٍ وَلاَ هَمٍّ وَلاَ حُزْنٍ وَلاَ أَذًى وَلاَ غَمٍّ حَتَّى الشَّوْكَةِ يُشَاكُهَا، إِلاَّ كَفَّرَ اللَّهُ بِهَا مِنْ خَطَايَاهُ ".
Narrated Abu Sa`id Al-Khudri and Abu Huraira:The Prophet (ﷺ) said, "No fatigue, nor disease, nor sorrow, nor sadness, nor hurt, nor distress befalls a Muslim, even if it were the prick he receives from a thorn, but that Allah expiates some of his sins for that
حَدَّثَنَا إِبْرَاهِيمُ بْنُ الْمُنْذِرِ، قَالَ حَدَّثَنِي مُحَمَّدُ بْنُ فُلَيْحٍ، قَالَ حَدَّثَنِي أَبِي، عَنْ هِلاَلِ بْنِ عَلِيٍّ، مِنْ بَنِي عَامِرِ بْنِ لُؤَىٍّ عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي هُرَيْرَةَ ـ رضى الله عنه ـ قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم " مَثَلُ الْمُؤْمِنِ كَمَثَلِ الْخَامَةِ مِنَ الزَّرْعِ مِنْ حَيْثُ أَتَتْهَا الرِّيحُ كَفَأَتْهَا، فَإِذَا اعْتَدَلَتْ تَكَفَّأُ بِالْبَلاَءِ، وَالْفَاجِرُ كَالأَرْزَةِ صَمَّاءَ مُعْتَدِلَةً حَتَّى يَقْصِمَهَا اللَّهُ إِذَا شَاءَ ".
Narrated Abu Huraira:Allah's Messenger (ﷺ) said, "The example of a believer is that of a fresh tender plant; from whatever direction the wind comes, it bends it, but when the wind becomes quiet, it becomes straight again. Similarly, a believer is afflicted with calamities (but he remains patient till Allah removes his difficulties.) And an impious wicked person is like a pine tree which keeps hard and straight till Allah cuts (breaks) it down when He wishes." (See Hadith No. 558, Vol)
حَدَّثَنَا مُحَمَّدُ بْنُ يَحْيَى، قال حَدَّثَنَا إِسْحَاقُ بْنُ مُحَمَّدٍ الْفَرْوِيُّ، قال حَدَّثَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عُمَارَةَ بْنِ غَزِيَّةَ، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنْ قَتَادَةَ بْنِ النُّعْمَانِ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ " إِذَا أَحَبَّ اللَّهُ عَبْدًا حَمَاهُ الدُّنْيَا كَمَا يَظَلُّ أَحَدُكُمْ يَحْمِي سَقِيمَهُ الْمَاءَ " . قَالَ أَبُو عِيسَى وَفِي الْبَابِ عَنْ صُهَيْبٍ وَأُمِّ الْمُنْذِرِ . وَهَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ . وَقَدْ رُوِيَ هَذَا الْحَدِيثُ عَنْ مَحْمُودِ بْنِ لَبِيدٍ عَنِ النَّبِيِّ صلى الله عليه وسلم مُرْسَلاً . حَدَّثَنَا عَلِيُّ بْنُ حُجْرٍ، قال أَخْبَرَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عَمْرِو بْنِ أَبِي عَمْرٍو، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنِ النَّبِيِّ صلى الله عليه وسلم نَحْوَهُ وَلَمْ يَذْكُرْ فِيهِ عَنْ قَتَادَةَ بْنِ النُّعْمَانِ . قَالَ أَبُو عِيسَى وَقَتَادَةُ بْنُ النُّعْمَانِ الظَّفَرِيُّ هُوَ أَخُو أَبِي سَعِيدٍ الْخُدْرِيِّ لأُمِّهِ وَمَحْمُودُ بْنُ لَبِيدٍ قَدْ أَدْرَكَ النَّبِيَّ صلى الله عليه وسلم وَرَآهُ وَهُوَ غُلاَمٌ صَغِيرٌ .
Qatadah bin An-Nu'man narrated that the Messenger of Allah (s.a.w) said:"When Allah loves a slave, He prevents him from the world, just as one of you prevents his sick from water." Another chain reports a similar narration
حَدَّثَنَا عَبَّاسُ بْنُ مُحَمَّدٍ الدُّورِيُّ، قال حَدَّثَنَا يُونُسُ بْنُ مُحَمَّدٍ، قال حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ عُثْمَانَ بْنِ عَبْدِ الرَّحْمَنِ التَّيْمِيِّ، عَنْ يَعْقُوبَ بْنِ أَبِي يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ، قَالَتْ دَخَلَ عَلَىَّ رَسُولُ اللَّهِ صلى الله عليه وسلم وَمَعَهُ عَلِيٌّ وَلَنَا دَوَالٍ مُعَلَّقَةٌ قَالَتْ فَجَعَلَ رَسُولُ اللَّهِ صلى الله عليه وسلم يَأْكُلُ وَعَلِيٌّ مَعَهُ يَأْكُلُ . فَقَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم لِعَلِيٍّ " مَهْ مَهْ يَا عَلِيُّ فَإِنَّكَ نَاقِهٌ " . قَالَ فَجَلَسَ عَلِيٌّ وَالنَّبِيُّ صلى الله عليه وسلم يَأْكُلُ . قَالَتْ فَجَعَلْتُ لَهُمْ سِلْقًا وَشَعِيرًا فَقَالَ النَّبِيُّ صلى الله عليه وسلم " يَا عَلِيُّ مِنْ هَذَا فَأَصِبْ فَإِنَّهُ أَوْفَقُ لَكَ " . قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ لاَ نَعْرِفُهُ إِلاَّ مِنْ حَدِيثِ فُلَيْحٍ . وَيُرْوَى عَنْ فُلَيْحٍ عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ . حَدَّثَنَا مُحَمَّدُ بْنُ بَشَّارٍ، قال حَدَّثَنَا أَبُو عَامِرٍ، وَأَبُو دَاوُدَ قَالاَ حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ، عَنْ يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ الأَنْصَارِيَّةِ، فِي حَدِيثِهِ قَالَتْ دَخَلَ عَلَيْنَا رَسُولُ اللَّهِ صلى الله عليه وسلم فَذَكَرَ نَحْوَ حَدِيثِ يُونُسَ بْنِ مُحَمَّدٍ إِلاَّ أَنَّهُ قَالَ " أَنْفَعُ لَكَ " . وَقَالَ مُحَمَّدُ بْنُ بَشَّارٍ وَحَدَّثَنِيهِ أَيُّوبُ بْنُ عَبْدِ الرَّحْمَنِ . هَذَا حَدِيثٌ جَيِّدٌ غَرِيبٌ .
Umm Al-Mundhir said:"The Messenger of Allah (ﷺ) entered upon me, while `Ali was with him, and we had a cluster of unripe dates hanging." She said: "The Messenger of Allah (ﷺ) began eating, and `Ali ate with him. The Messenger of Allah (ﷺ) said to `Ali: 'Stop, stop, for you are still recovering.' So `Ali sat and the Prophet (ﷺ) ate." She said: "I made some chard and barley for them, so the Prophet (ﷺ) said: 'O `Ali eat from this, for indeed it will be more suitable for you." Another chain reports a similar narration
Arabic originals, reached through the subject’s Arabic senses. Interpretive sources, never proof of a ruling.
62 الثالث عن ابن عباس رضي الله عنهما قال كنت خلف النبي صلى الله عليه وسلم يوما فقال يا غلام إني أعلمك كلمات احفظ الله يحفظك احفظ الله تجده تجاهك إذا سألت فاسأل الله وإذا استعنت فاستعن بالله واعلم أن الأمة لو اجتمعت على أن ينفعوك بشيء لم ينفعوك إلا بشيء قد كتبه الله لك وإن اجتمعوا على أن يضروك بشيء لم يضروك إلا بشيء قد كتبه الله عليك رفعت الأقلام وجفت الصحف رواه الترمذي وقال حديث حسن صحيح وفي رواية غير الترمذي احفظ الله تجده أمامك تعرف إلى الله في الرخاء يعرفك في الشدة واعلم أن ما أخطأك لم يكن ليصيبك وما أصابك لم يكن ليخطئك واعلم أن النصر مع الصبر وأن الفرج مع الكرب وأن مع العسر يسرا
التاسعة والخمسون ان ذكر الله عز وجل يسهل الصعب وييسر العسير ويخفف المشاق فما ذكر الله عز وجل على صعب الا هان ولا على عسير الا تيسر ولا مشقة الا خفت ولا شدة الا زالت ولا كربه الا انفرجت فذكر الله تعالى هو الفرج بعد الشدة واليسر بعد العسر والفرج بعد الغم والهم يوضحه
وقالت أسماء بنت عميس : علمني رسول اللهكلمات أقولها عند الكرب : الله الله ربي لا أشرك به شيئا
التنفيس هو الترويح يقال نفس الله عنك الكرب أي اراحك منه وفي الحديث الصحيح من نفس عن مؤمن كربة من كرب الدنيا نفس الله عنه كربة من كرب يوم القيامة
وفى "صحيح البخاري" من حديث أنس رضي الله عنه قال: لما ثقل النبي صلى الله عليه وآله وسلم، جعل يتغشاه الكرب، فقالت فاطمة رضي الله عنها: واكرب أبتاه! فقال لها: "ليس على أبيك كرب بعد اليوم".
خليلي ما من ساعة تذكرانها % من الدهر إلا فرجت عني الكربا
Peer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.
Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.: Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life st
The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.: Objective: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30) or pla
The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials.: Objective: This study was conducted to assess the effect of Nigella sativa (N. sativa) supplementation on inflammatory and oxidative markers among the adult population. Methods: We carried out a comprehensive, systematic search of Scopus, Embase, Cochrane Library, Web of Science, PubMed, and Google Scholar till December 2022. A random-effects model was used to estimate the overall effect size. Results: In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Fi
Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrat
Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.: Background: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. Methods: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, s
Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review.: Background: The aim of this article was to perform a systematic review of studies investigating the association between peripheral levels of cytokines and C-reactive protein (CRP), cytokine gene polymorphisms and cognition in patients with schizophrenia and bipolar disorder (BD). Methods: The following databases: PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source: Nursing/Academic Edition databases were searched according to the PRISMA guidelines. We included studies that
Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases.
Aging gradually decreases cellular biological functions and increases the risk of age-related diseases. Cancer, type 2 diabetes mellitus, cardiovascular disease, and neurological disorders are commonly classified as age-related diseases that can affect the lifespan and health of individuals. Aging is a complicated and sophisticated biological process involving damage to biochemical macromolecules including DNA, proteins, and cellular organelles such as mitochondria. Aging causes multiple alterations in biological processes including energy metabolism and nutrient sensing, thus reducing cell proliferation and causing cellular senescence. Among the polyphenolic phytochemicals, resveratrol is believed to reduce the negative effects of the aging process through its multiple biological activities. Resveratrol increases the lifespan of several model organisms by regulating oxidative stress, en…
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A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols.
Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world's most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) a…
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Oxidative stress in alzheimer's disease: A review on emergent natural polyphenolic therapeutics.
Objectives: The aim of this research was to review the literature on Alzheimer's disease (AD) with a focus on polyphenolics as antioxidant therapeutics. Design: This review included a search of the literature up to and including September 2019 in PubMed and MEDLINE databases using search terms that included: Alzheimer's Disease, Aβ peptide, tau, oxidative stress, redox, oxidation, therapeutic, antioxidant, natural therapy, polyphenol. Any review articles, case studies, research reports and articles in English were identified and subsequently interrogated. Citations within relevant articles were also examined for consideration in this review. Results: Alzheimer's disease is a neurodegenerative disorder that is clinically characterised by the progressive deterioration of cognitive functions and drastic changes in behaviour and personality. Due to the significant presence of oxidative damag…
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Gut Microbiota and Dysbiosis in Alzheimer's Disease: Implications for Pathogenesis and Treatment.
Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term "microbiota-gut-brain axis" from "gut-brain axis" underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer's disease (AD). Illustration of the mechanisms underlying the regulation by gut microb…
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The tortuous path of lactate shuttle discovery: From cinders and boards to the lab and ICU.
Once thought to be a waste product of oxygen limited (anaerobic) metabolism, lactate is now known to form continuously under fully oxygenated (aerobic) conditions. Lactate shuttling between producer (driver) and consumer cells fulfills at least 3 purposes; lactate is: (1) a major energy source, (2) the major gluconeogenic precursor, and (3) a signaling molecule. The Lactate Shuttle theory is applicable to diverse fields such as sports nutrition and hydration, resuscitation from acidosis and Dengue, treatment of traumatic brain injury, maintenance of glycemia, reduction of inflammation, cardiac support in heart failure and following a myocardial infarction, and to improve cognition. Yet, dysregulated lactate shuttling disrupts metabolic flexibility, and worse, supports oncogenesis. Lactate production in cancer (the Warburg effect) is involved in all main sequela for carcinogenesis: angiog…
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A review of antibiotics, depression, and the gut microbiome.
Emerging evidence indicates that disruption of the intestinal flora play an important role in the pathogenesis of depression. As one of the causes of such disturbances, the role of antibiotics in depression risk is gradually being revealed. Herein, we review recent findings showing that the use of both single and multiple antibiotic regimens may be related to depression by changing the gut microbiota and the brain-gut axis. Based on recent discoveries, we also suggest that several brain-gut interactive mechanisms (particularly those involving nerve and glial cells, neurotransmitters, brain neurotrophic factors, inflammatory factors, short-chain fatty acids, circulating metabolites, blood-brain barrier, and oxidative stress) may help understand the effects of antibiotics on intestinal flora and its relationship with depression.
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COVID-19 and the elderly: insights into pathogenesis and clinical decision-making.
The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.
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On the irrelevancy of hydroxyl radical to DNA damage from oxidative stress and implications for epigenetics.
Contrary to frequent reports in the literature, hydroxyl radical is not a key species participating in endogenous oxidative DNA damage. Instead, carbonate radical anion is formed from the Fenton reaction under cellular conditions and from decomposition of nitrosoperoxycarbonate generated during inflammation. Carbonate radical anion is a potent one-electron oxidant capable of generating base radical cations that can migrate over long distances in duplex DNA, ultimately generating 8-oxo-7,8-dihydroguanine at a redox-sensitive sequence such as GGG. Such a mechanism enables G-quadruplex-forming sequences to act as long-range sensors of oxidative stress, impacting gene expression via the DNA repair mechanism that reads and ultimately erases the oxidized base. With a writing, reading and erasing mechanism in place, oxidative 'damage' to DNA might be relabeled as 'epigenetic' modifications.
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The Role of Opioid Receptors in Immune System Function.
Research on the effects of opioids on immune responses was stimulated in the 1980s by the intersection of use of intravenous heroin and HIV infection, to determine if opioids were enhancing HIV progression. The majority of experiments administering opioid alkaloids (morphine and heroin) in vivo, or adding these drugs to cell cultures in vitro, showed that they were immunosuppressive. Immunosuppression was reported as down-regulation: of Natural Killer cell activity; of responses of T and B cells to mitogens; of antibody formation in vivo and in vitro; of depression of phagocytic and microbicidal activity of neutrophils and macrophages; of cytokine and chemokine production by macrophages, microglia, and astrocytes; by sensitization to various infections using animal models; and by enhanced replication of HIV in vitro. The specificity of the receptor involved in the immunosuppression was s…
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Drugs in Development for Acute Kidney Injury.
The care of patients with acute kidney injury (AKI) has been limited due to the lack of effective therapeutics that can either prevent AKI during high-risk situations or treat AKI once established. A revolution in the scientific understanding of the pathogenesis of AKI has led to the identification of potential therapeutic targets. These targets include pathways involved in inflammation, cellular repair and fibrosis, cellular metabolism and mitochondrial function, oxidative stress, apoptosis, and hemodynamics and oxygen delivery. Many compounds are entering early-phase clinical trials. In addition, efforts to better describe sub-categories of AKI (through endo-phenotyping) hold promise to target therapies more effectively based upon pathways that are operative in the pathogenesis. These advances bring optimism that the care of patients with AKI will be transformed with the hope of better…
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Understanding diversity in oxidative status and oxidative stress: the opportunities and challenges ahead.
Oxidative stress may be of profound biological relevance. In this Commentary, I discuss some key issues faced by the emerging field of oxidative stress ecology, and seek to provide interpretations and solutions. First, I show that the way in which we define oxidative stress has far-reaching implications for the interpretation of results, and that we need to distinguish between (1) a biochemical definition in terms of the molecular outcomes of oxidative stress (e.g. generation of oxidative damage) and (2) a biological definition in terms of the fitness consequences for the organism (e.g. effects on fertility). Second, I discuss the dangers of comparing different tissues and markers. Third, I highlight the need to pay more attention to the cross-talk between oxidative stress and other important physiological costs and functions; this will allow us to better understand the mechanistic basis…
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Hallmarks of senescence and aging.
The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable mea…
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The Influence of Antidepressants on the Immune System.
Depression is one of the most frequently diagnosed condition in psychiatry. Despite the availability of many preparations, over 30% of treated patients do not achieve remission. Recently the emphasis is put on the contribution of the body's inflammatory response as one of the causes of depression. The interactions between nervous and immune systems are the main issue addressed by psychoneuroimmunology. In patients suffering from depression changes in the plasma concentrations of cytokines and in the number and level of activation of immune cells has been found. Attention is paid to the high levels of pro-inflammatory cytokines, the prevalence of Th1 responses to Th2, weakening of NK cell cytotoxicity and changes in lymphocyte proliferation and apoptosis. A number of studies focus on influence of antidepressants and non-standard methods of depression treatment, such as ketamine infusion, …
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The impact of heat stress on the immune system in dairy cattle: A review.
Heat stress is well documented to have a negative influence on livestock productivity and these impacts may be exacerbated by climate change. Dairy cattle can be more vulnerable to the negative effects of heat stress as these adverse impacts may be more profound during pregnancy and lactation. New emerging diseases are usually linked to a positive relationship with climate change and the survival of microrganisms and/or their vectors. These diseases may exaggerate the immune suppression associated with the immune suppressive effect of heat stress that is mediated by the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axes. It has been established that heat stress has a negative impact on the immune system via cell mediated and humoral immune responses. Heat stress activates the HPA axis and increases peripheral levels of glucocorticoids subsequently suppr…
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Physical Exercise Inhibits Inflammation and Microglial Activation.
Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates multiple systems that are known to regulate neuroinflammation and glial activation. Activated microglia and several pro-inflammatory cytokines play active roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The purpose of this review is to highlight the impacts of exercise on microglial activation. Possible mechanisms involved in exercise-modulated microglial activation are also discussed. Undoubtedly, more studies are needed in order to disclose the detailed mechanisms, but this approach offers therapeutic potential for improving the brain health of millions of aging people where pharmacological …
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A Review on the Protective Effects of Honey against Metabolic Syndrome.
Metabolic syndrome (MetS) is a cluster of diseases comprising of obesity, diabetes mellitus, dyslipidemia, and hypertension. There are numerous pre-clinical as well as human studies reporting the protective effects of honey against MetS. Honey is a nutritional food low in glycemic index. Honey intake reduces blood sugar levels and prevents excessive weight gain. It also improves lipid metabolism by reducing total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL), which leads to decreased risk of atherogenesis. In addition, honey enhances insulin sensitivity that further stabilizes blood glucose levels and protects the pancreas from overstimulation brought on by insulin resistance. Furthermore, antioxidative properties of honey help in reducing oxidative stress, which is one of the central mechanisms in MetS. Lastly, honey pro…
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Intermittent Fasting: Is the Wait Worth the Weight?
Purpose of review: We review the underlying mechanisms and potential benefits of intermittent fasting (IF) from animal models and recent clinical trials. Recent findings: Numerous variations of IF exist, and study protocols vary greatly in their interpretations of this weight loss trend. Most human IF studies result in minimal weight loss and marginal improvements in metabolic biomarkers, though outcomes vary. Some animal models have found that IF reduces oxidative stress, improves cognition, and delays aging. Additionally, IF has anti-inflammatory effects, promotes autophagy, and benefits the gut microbiome. The benefit-to-harm ratio varies by model, IF protocol, age at initiation, and duration. We provide an integrated perspective on potential benefits of IF as well as key areas for future investigation. In clinical trials, caloric restriction and IF result in similar degrees of weight…
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The fetal programming of telomere biology hypothesis: an update.
Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setti…
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Stress Biomarkers in Biological Fluids and Their Point-of-Use Detection.
Hormones produced by glands in the endocrine system and neurotransmitters produced by the nervous system control many bodily functions. The concentrations of these molecules in the body are an indication of its state, hence the use of the term biomarker. Excess concentrations of biomarkers, such as cortisol, serotonin, epinephrine, and dopamine, are released by the body in response to a variety of conditions, for example, emotional state (euphoria, stress) and disease. The development of simple, low-cost modalities for point-of-use (PoU) measurements of biomarkers levels in various bodily fluids (blood, urine, sweat, saliva) as opposed to conventional hospital or lab settings is receiving increasing attention. This paper starts with a review of the basic properties of 12 primary stress-induced biomarkers: origin in the body (i.e., if they are produced as hormones, neurotransmitters, or b…
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Telomeres, Telomerase and Ageing.
Telomeres are specialised structures at the end of linear chromosomes. They consist of tandem repeats of the hexanucleotide sequence TTAGGG, as well as a protein complex called shelterin. Together, they form a protective loop structure against chromosome fusion and degradation. Shortening or damage to telomeres and opening of the loop induce an uncapped state that triggers a DNA damage response resulting in senescence or apoptosis. Average telomere length, usually measured in human blood lymphocytes, was thought to be a biomarker for ageing, survival and mortality. However, it becomes obvious that regulation of telomere length is very complex and involves multiple processes. For example, the "end replication problem" during DNA replication as well as oxidative stress are responsible for the shortening of telomeres. In contrast, telomerase activity can potentially counteract telomere shor…
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Physical activity and telomere length: Impact of aging and potential mechanisms of action.
Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exer…
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The Microbiome-Gut-Brain Axis in Health and Disease.
Gut microbes are capable of producing most neurotransmitters found in the human brain. Evidence is accumulating to support the view that gut microbes influence central neurochemistry and behavior. Irritable bowel syndrome is regarded as the prototypic disorder of the brain-gut-microbiota axis that can be responsive to probiotic therapy. Translational studies indicate that certain bacteria may have an impact on stress responses and cognitive functioning. Manipulating the gut microbiota with psychobiotics, prebiotics, or even antibiotics offers a novel approach to altering brain function and treating gut-brain axis disorders, such as depression and autism.
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Unraveling the metabolic health benefits of fasting related to religious beliefs: A narrative review.
Periodic fasting, under a religious aspect, has been adopted by humans for centuries as a crucial pathway of spiritual purification. Caloric restriction, with or without exclusion of certain types of food, is often a key component. Fasting varies significantly among different populations according to cultural habits and local climate conditions. Religious fasting in terms of patterns (continuous versus intermittent) and duration can vary from 1 to 200 d; thus, the positive and negative impact on health can be considerable. Advantages of religious fasting are claimed by many but have been explored mainly by a limited number of studies conducted in Buddhist, Christian, or Muslim populations. These trials indicate that religious fasting has beneficial effects on body weight and glycemia, cardiometabolic risk markers, and oxidative stress parameters. Animals exposed to a diet mimicking fasti…
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Mechanisms of hepatic stellate cell activation.
Hepatic fibrosis is a dynamic process characterized by the net accumulation of extracellular matrix resulting from chronic liver injury of any aetiology, including viral infection, alcoholic liver disease and NASH. Activation of hepatic stellate cells (HSCs) - transdifferentiation of quiescent, vitamin-A-storing cells into proliferative, fibrogenic myofibroblasts - is now well established as a central driver of fibrosis in experimental and human liver injury. Yet, the continued discovery of novel pathways and mediators, including autophagy, endoplasmic reticulum stress, oxidative stress, retinol and cholesterol metabolism, epigenetics and receptor-mediated signals, reveals the complexity of HSC activation. Extracellular signals from resident and inflammatory cells including macrophages, hepatocytes, liver sinusoidal endothelial cells, natural killer cells, natural killer T cells, platelet…
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Molecular and physiological manifestations and measurement of aging in humans.
Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging …
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