Stress physiology and inflammation

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’

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

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

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

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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

Muscle damage, inflammatory, immune and performance responses to three football games in 1 week in competitive male players.

Purpose: We examined effects of a three-game, 1-week microcycle (G1, G2, G3) on recovery of performance and inflammatory responses in professional male footballers. Methods: Players were randomized into an experimental (EXP; N = 20) and a control group (CON; N = 20). Blood was drawn and repeated sprint ability (RSA), muscle soreness and knee range of motion (KJRM) were determined pre- and post-games and during recovery. Results: High-intensity running during G2 was 7-14% less compared to G1 and G3. RSA declined in EXP by 2-9% 3 days post-game with G2 causing the greatest performance impairment. In EXP, game play increased muscle soreness (~sevenfold) compared to CON with G2 inducing the greatest rise, while KJRM was attenuated post-game in EXP compared to CON (5-7%) and recovered slower post G2 and G3 than G1. CK, CRP, sVCAM-1, sP-Selectin and cortisol peaked 48 h post-games with G2 elic…

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The thymoquinone-induced production of reactive oxygen species promotes dedifferentiation through the ERK pathway and inflammation through the p38 and PI3K pathways in rabbit articular chondrocytes.

Dedifferentiation and inflammation are major features of cartilage degeneration during the pathogenesis of osteoarthritis (OA). Thymoquinone (TQ) is the major compound of black seed oil isolated from Nigella sativa with various beneficial or harmful effects on several diseases; however, its effects on the dedifferentiation and inflammation of chondrocytes have not yet been characterized. In the present study, we investigated whether TQ regulates the dedifferentiation and inflammation of rabbit articular chondrocytes, focusing on the production of reactive oxygen species (ROS) in rabbit articular chondrocytes. TQ induced the generation of ROS in a dose-dependent manner, as shown by staining with the fluorescent probe, 2'-7'-dichlorofluorescein diacetate. We confirmed that TQ induced dedifferentiation by measuring the loss of type II collagen and the reduction in chondroitin sulfate proteo…

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Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells.

Background: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. Methods: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or…

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Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.

To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capabi…

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Heat stress-induced memory impairment is associated with neuroinflammation in mice.

Background: Heat stress induces many pathophysiological responses and has a profound impact on brain structure. It has been demonstrated that exposure to high temperature induces cognitive impairment in experimental animals and humans. Although the effects of heat stress have long been studied, the mechanisms by which heat stress affects brain structure and cognition not well understood. Methods: In our longitudinal study of mice exposed to heat over 7, 14, or 42 days, we found that heat stress time dependently impaired cognitive function as determined by Y-maze, passive avoidance, and novel object recognition tests. To elucidate the histological mechanism by which thermal stress inhibited cognitive abilities, we examined heat stress-induced inflammation in the hippocampus. Results: In mice subjected to heat exposure, we found: 1) an increased number of glial fibrillary acid protein (GFA…

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Loneliness, eudaimonia, and the human conserved transcriptional response to adversity.

Background: Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression-the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life). Methods: Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retiremen…

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A feasibility study of the association of exposure to biomass smoke with vascular function, inflammation, and cellular aging.

Background: Biomass smoke at higher concentrations is associated with respiratory symptoms and, after years of exposure, increased risk of respiratory disorders in adults, but its effects on cardiovascular diseases are not well characterized, particularly compared with other pollution sources like tobacco smoke or traffic. Methods: We conducted a cross-sectional study and enrolled 25 women living in rural Sichuan, China. We measured integrated 24-h personal exposure to fine particulate matter (PM2.5) and black carbon, and measured PM2.5 and black carbon in their kitchens. We assessed participants' brachial and central blood pressure and arterial stiffness using pulse wave analysis, and analyzed dried blood spot and buccal cell samples for C-reactive protein and relative telomere length. We also evaluated the difference in these physiological and biomarker measures between individuals wit…

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Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180.

Unlabelled: It remains unclear how different translocator protein (TSPO) ligands reflect the spatial extent of astrocyte or microglial activation in various neuroinflammatory conditions. Here, we use a reproducible lipopolysaccharide (LPS)-induced model of acute central nervous system inflammation to compare the binding performance of a new TSPO ligand (18)F-GE-180 with (11)C-(R)-PK11195. Using immunohistochemistry, we also explore the ability of the TSPO ligands to detect activated microglial cells and astrocytes. Methods: Lewis rats (n = 30) were microinjected with LPS (1 or 10 μg) or saline (1 μL) into the left striatum. The animals were imaged in vivo at 16 h after the injection using PET radiotracers (18)F-GE-180 or (11)C-(R)-PK11195 (n = 3 in each group) and were killed afterward for autoradiography of the brain. Immunohistochemical assessment of OX-42 and glial fibrillary acidic p…

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Spinal cord injury causes brain inflammation associated with cognitive and affective changes: role of cell cycle pathways.

Experimental spinal cord injury (SCI) causes chronic neuropathic pain associated with inflammatory changes in thalamic pain regulatory sites. Our recent studies examining chronic pain mechanisms after rodent SCI showed chronic inflammatory changes not only in thalamus, but also in other regions including hippocampus and cerebral cortex. Because changes appeared similar to those in our rodent TBI models that are associated with neurodegeneration and neurobehavioral dysfunction, we examined effects of mouse SCI on cognition, depressive-like behavior, and brain inflammation. SCI caused spatial and retention memory impairment and depressive-like behavior, as evidenced by poor performance in the Morris water maze, Y-maze, novel objective recognition, step-down passive avoidance, tail suspension, and sucrose preference tests. SCI caused chronic microglial activation in the hippocampus and cere…

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NIDDK international conference report on diabetes and depression: current understanding and future directions.

Comorbid diabetes and depression are a major clinical challenge as the outcomes of each condition are worsened by the other. This article is based on the presentations and discussions during an international meeting on diabetes and depression convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression. While the psychological burden of diabetes may contribute to depression in some cases, this explanation does not sufficiently explain the relationship between these two conditions. Shared biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors, are important to consider in understa…

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Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.

Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24-h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was perform…

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Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods.

Purpose: Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. In search of anti-inflammatory foods, we have systematically screened a variety of common dietary plants and mushrooms for their anti-inflammatory activity. Methods: A selection of 115 samples was prepared by a generic food-compatible processing method involving heating. These products were tested for their anti-inflammatory activity in murine N11 microglia and RAW 264.7 macrophages, using nitric oxide (NO) and tumour necrosis factor-α (TNF-α) as pro-inflammatory readouts. Results: Ten food samples including lime zest, English breakfast tea, honey-brown mushroom, button mushroom, oyster mushroom, cinnamon and cloves inhibited NO production in N11 microglia, with IC50 values below 0.5 mg/ml. The most active samples were onion, oregano and red sweet potato, exhibiting IC50 values below 0.1 …

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Pro-/anti-inflammatory dysregulation in patients with first episode of psychosis: toward an integrative inflammatory hypothesis of schizophrenia.

Background: Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. Methods: Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. Results: Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression anal…

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Loneliness promotes inflammation during acute stress.

Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In our first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-α) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1β) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-α in Study 2, although the result was i…

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Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction.

Myocardial infarction (MI) leads to rapid necrosis of cardiac myocytes. To achieve tissue integrity and function, inflammatory cells are activated, including monocytes/macrophages. However, the effect of monocyte/macrophage recruitment after MI remains poorly defined. After experimental MI, monocytes and macrophages were depleted through serial injections of clodronate-containing liposomes. Monocyte/macrophage infiltration was reduced in the myocardium after MI by active treatment. Mortality was increased due to thromboembolic events in monocyte- and macrophage-depleted animals (92 vs. 33%; P<0.01). Left ventricular thrombi were detectable as early as 24 h after MI; this was reproduced in a genetic model of monocyte/macrophage ablation. A general prothrombotic state, increased infarct expansion, and deficient neovascularization were not observed. Severely compromised extracellular matrix…

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Involvement of MAPK/NF-κB signaling in the activation of the cholinergic anti-inflammatory pathway in experimental colitis by chronic vagus nerve stimulation.

Background: Autonomic nervous system dysfunction is implicated in the etiopathogenesis of inflammatory bowel diseases (IBD). Therapies that increase cardiovagal activity, such as Mind-Body interventions, are currently confirmed to be effective in clinical trials in IBD. However, a poor understanding of pathophysiological mechanisms limits the popularization of therapies in clinical practice. The aim of the present study was to explore the mechanisms of these therapies against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats using a chronic vagus nerve stimulation model in vivo, as well as the lipopolysaccharide (LPS)-induced inflammatory response in human epithelial colorectal adenocarcinoma cells (Caco-2) by acetylcholine in vitro. Methods and results: Colitis was induced in rats with rectal instillation of TNBS, and the effect of chronic VNS (0.25 mA, 20 Hz, 500 ms) on…

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Social isolation and adult mortality: the role of chronic inflammation and sex differences.

The health and survival benefits of social embeddedness have been widely documented across social species, but the underlying biophysiological mechanisms have not been elucidated in the general population. We assessed the process by which social isolation increases the risk for all-cause and chronic disease mortality through proinflammatory mechanisms. Using the 18-year mortality follow-up data (n = 6,729) from the National Health and Nutrition Examination Survey (1988-2006) on Social Network Index and multiple markers of chronic inflammation, we conducted survival analyses and found evidence that supports the mediation role of chronic inflammation in the link between social isolation and mortality. A high-risk fibrinogen level and cumulative inflammation burden may be particularly important in this link. There are notable sex differences in the mortality effects of social isolation in t…

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Mediterranean diet, telomere maintenance and health status among elderly.

Leukocyte telomere length (LTL) and rate of telomere shortening are known biomarkers of aging while, numerous studies showed that Mediterranean diet (MD) may boost longevity. We studied association between telomere length, telomerase activity and different adherence to MD and its effects on healthy status. The study was conducted in 217 elderly subjects stratified according Mediterranean diet score (MDS) in low adherence (MDS≤3), medium adherence (MDS 4-5) and high adherence (MDS≥6) groups. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. High adherence group showed longer LTL (p = 0.003) and higher telomerase activity (p = 0.013) compared to others. Linear regression analysis including age, gender, smoking habit and MDS showed that MDS was independently associated with LTL (p = 0.024) and telomerase activity levels (p = 0.006). …

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α7 nicotinic acetylcholine receptor (α7nAChR) expression in bone marrow-derived non-T cells is required for the inflammatory reflex.

The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow-derived cells significantly impaired vagus nerve-mediated regulation of tumor necrosis factor …

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17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception.

Background and purpose: Transient receptor potential ion channel vanilloid 3 (TRPV3) is expressed in skin keratinocytes and plays an important role in thermal and chemical nociceptions in the periphery. The presence of TRPV3 inhibitors would improve our understanding of TRPV3 function and help to develop receptor-specific analgesics. However, little is known about physiological substances that specifically inhibit TRPV3 activity. Here, we investigated whether 17(R)-resolvin D1 (17R-RvD1), a naturally occurring pro-resolving lipid specifically affects TRPV3 activity. Experimental approach: We examined the effect of 17R-RvD1 on sensory TRP channels using Ca(2+) imaging and whole cell electrophysiology experiments in a HEK cell heterologous expression system, cultured sensory neurons and keratinocytes. We also examined changes in sensory TRP agonist-specific acute licking/flicking or flinch…

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Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation.

Although hepatic encephalopathy (HE) is linked to the gut microbiota, stool microbiome analysis has not found differences between HE and no-HE patients. This study aimed to compare sigmoid mucosal microbiome of cirrhotic patients to controls, between HE vs. no-HE patients, and to study their linkage with cognition and inflammation. Sixty cirrhotic patients (36 HE and 24 no-HE) underwent cognitive testing, stool collection, cytokine (Th1, Th2, Th17, and innate immunity), and endotoxin analysis. Thirty-six patients (19 HE and 17 no-HE) and 17 age-matched controls underwent sigmoid biopsies. Multitag pyrosequencing (including autochthonous genera, i.e., Blautia, Roseburia, Fecalibacterium, Dorea) was performed on stool and mucosa. Stool and mucosal microbiome differences within/between groups and correlation network analyses were performed. Controls had significantly higher autochthonous an…

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Neural regulation of inflammation: no neural connection from the vagus to splenic sympathetic neurons.

The 'inflammatory reflex' acts through efferent neural connections from the central nervous system to lymphoid organs, particularly the spleen, that suppress the production of inflammatory cytokines. Stimulation of the efferent vagus has been shown to suppress inflammation in a manner dependent on the spleen and splenic nerves. The vagus does not innervate the spleen, so a synaptic connection from vagal preganglionic neurons to splenic sympathetic postganglionic neurons was suggested. We tested this idea in rats. In a preparatory operation, the anterograde tracer DiI was injected bilaterally into the dorsal motor nucleus of vagus and the retrograde tracer Fast Blue was injected into the spleen. On histological analysis 7-9 weeks later, 883 neurons were retrogradely labelled from the spleen with Fast Blue as follows: 89% in the suprarenal ganglia (65% left, 24% right); 11% in the left coe…

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Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis.

Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (-28%), and mature, microtubule-associated protein-2-positive neurons (-36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1β resulted in an increase in…

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Schizophrenia genes, epigenetics and psychoneuroimmunology therapeutics: all make sense now?

Genetics, epigenetics, infection as an environmental factor, functional findings for the immune system, and a therapeutic approach with anti-inflammatory therapy provide evidence for a pivotal role of the immune system in schizophrenia. This field, therefore, should focus more on further schizophrenia research.

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Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.

Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, requi…

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