[Formation of hair and restoration of its innervation in human skin transplantation].
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Hair↗
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[The development of hair and the restoration of innervation in the skin transplants in man].
Various areas in 7 local flaps and in 6 free skin grafts from the back, abdomen and thigh, applied to the palm and fingers and retained for periods extending from several months to 17 years are studied. After the second year, the transplants display virtually complete recovery of the sensation for pain, touch, pressure and temperature. The hair roots in the transplants have varying thickness and reveal changes in the structure of the connective-tissue and outer epithelial sheath (Figs. 1, 2). The sebaceous glands are enlarged. Isolated sebaceous glands are encountered which do not communicate with the hair roots. In the upper layers of the corium bundles of myelin nerve fibers are observed, giving off small groups of 2-4 fibers each, with slightly ascending direction relative to the hair roots (Fig. 3). The nerve fibers break down into branches which are furthermore ramified into smaller branches, forming palisade-like endings along the outer epethelial sheath of the hair root (Figs. 4-8). They number 15-25, being usually thin, with a discrete number of thickenings, and resemble the normal fibers running along the hair roots of the donor site (Figs. 9, 10). No capsulated receptors, characteristic of the surrounding skin, are noted in the transplants. Hence, it is assumed that most likely, the endings of the regenerated nerve fibers along the hair roots, although uncapsulated and with identical structure, provide for perceiving the types of sensation, inherent of the hairy and glabrous human skin.
Female↗
Aging of hair follicle stem cells and their niche: mechanisms and regenerative therapeutic strategies.
Hair follicles (HFs) are vital skin appendages that perform fundamental functions including protection, thermoregulation, and sensation. Orchestrated by hair follicle stem cells (HFSCs), HFs undergo cyclic regeneration throughout the lifespan. However, during chronological aging, this mini-organ experiences progressive physiological decline, clinically characterized by a marked reduction in hair density and hair graying due to pigmentation dysfunction. This aging process involves HFSC exhaustion accompanied by diminished regenerative potential and differentiation capacity, leading to degenerative changes in the bulge architecture. Concurrently, the niche supporting HFSC homeostasis undergoes multi-dimensional and systemic degradation. This niche deterioration disrupts the delicate balance between HFSC quiescence and activation, further impeding hair regeneration. In this review, we delineate the dynamic anatomical changes throughout the hair growth cycle and describe the alterations of HFSCs during aging. We specifically focus on the mechanisms underlying the multi-dimensional degradation of the HFSC niche at tissue, cellular, and molecular levels. Furthermore, we discuss various therapeutic strategies aimed at ameliorating HF aging, offering potential insights for future clinical translation in hair regeneration. Finally, we propose that integrating spatiotemporal high-resolution technologies with genomic data to further decipher the spatiotemporal behaviors of aging HFSCs and niche cells will facilitate the establishment of a robust mechanistic framework for HFSC and niche aging.
Hair Follicle↗
Hair zinc compared with plasma zinc in uremic patients before and during regular hemodialysis.
Plasma and hair zinc concentrations were measured by atomic absorption spectrophotometry in 34 control subjects, 20 nondialyzed uremic patients and 18 patients treated with regular hemodialysis. Plasma zinc levels were low in both nondialyzed and hemodialyzed patients. Hair zinc levels were low in the nondialyzed uremics, but at least partialy restored to normal in patients on hemodialysis. In both patient groups, hair zinc was positively correlated with plasma zinc. In the nondialyzed patients haie zinc depletion in end-stage renal disease progresses with increasing degree of renal insufficiency and tends to be reversed by regular hemodialysis.
Adult↗
A base editor for the long-term restoration of auditory function in mice with recessive profound deafness.
A prevalent recessive mutation (c.2485C>T, p.Q829X) within the OTOF gene leads to profound prelingual hearing loss. Here we show that in Otof mice harbouring a mutation (c.2482C>T, p.Q828X) homozygous to human OTOF that faithfully mimics the hearing-loss phenotype, a base editor (consisting of the deaminase ABE7.10max and the Cas9 variant SpCas9-NG) packaged in adeno-associated viruses and injected into the inner ear of the mice via the round-window membrane effectively corrected the pathogenic mutation, with no apparent off-target effects. The treatment restored the levels of the otoferlin protein in 88% of the inner hair cells and stably rescued the auditory function of the mice to near-wild-type levels for over 1.5 years while improving synaptic exocytosis in the inner hair cells. We also show that an adenine base editor that targets the prevalent human OTOF mutation restored hearing in humanized mice to levels comparable to those of the wild-type counterparts. Base editors may be effective for the treatment of hereditary deafness.
Animals↗
Hair growth cycles and wave patterns in "nude" mice.
Hair growth cycles and waves were studied through five generations of hair growth in C57BL/6Icr "nude" mice. One group of nudes received thymus grafts, a second group was composed of athymid nudes and a third consisted of heterozygous (nu/&) haired littermates. The results showed that hair growth cycles and wave patterns were essentially the same in thymus-restored nudes and athymic nudes which indicated that thymus did not play a role in these phenomena. The time interval between hair cycles was considerably shorter in both groups of nude mice as compared to heterozygotes (nu/&). Finally, the hair growth wave pattern in nude mice did not change throughout the generation of hair growth whereas profound changes in wave patterns were observed in heterozygous (nu/&) littermates.
Animals↗
Schisantherin B mitigates cisplatin-induced ototoxicity by modulating the CNPY2-PERK/CHOP signaling axis.
Irreversible cisplatin-induced hearing loss (CIHL) is a refractory chemotherapy-related adverse effect with limited clinical treatments. Schisantherin B (STB), a lignan isolated from Schisandra chinensis, is widely recognized for its neuroprotective properties, while its role in auditory injury remains unclear. Herein, we found that STB alleviated cisplatin-induced ototoxicity in House Ear Institute Organ of Corti 1 (HEI-OC1) cells and guinea pig models, protecting cochlear hair cells, synaptic ribbons and spiral ganglion neurons, and partially restoring auditory brainstem response (ABR) thresholds. Furthermore, combined drug affinity responsive target stability (DARTS) assay, the cellular thermal shift assay (CETSA), and the surface plasmon resonance (SPR) assay, we confirmed STB directly binds to the canopy FGF signaling regulator 2 (CNPY2), a key initiator of endoplasmic reticulum (ER) stress. Notably, consistent dual in vitro and in vivo validation confirmed that STB exerts no regulatory effect on CNPY2 protein abundance, yet suppressed the downstream Protein kinase R-like endoplasmic reticulum kinase / C/EBP homologous protein (PERK/CHOP) signaling cascade and ER stress-mediated apoptosis. Moreover, molecular docking and co-immunoprecipitation (co-IP) validated the physical binding of STB to CNPY2 and the endogenous interaction between CNPY2 and PERK. Additionally, CNPY2 overexpression and shRNA knockdown further verified this functional relationship. Integrated proteomic and transcriptomic analyses showed STB partially reversed cisplatin-triggered inflammation and excessive ER stress. Collectively, our results suggest STB may serve as a potential otoprotective agent. The CNPY2-PERK/CHOP axis is closely linked to cisplatin-induced cochlear damage and offers a feasible target for intervention against CIHL. Abbreviations: CIHL, cisplatin-induced hearing loss; STB, Schisantherin B; HEI-OC1, house ear institute organ of corti 1; ABR, auditory brainstem response; DARTS, drug affinity responsive target stability; CETSA, cellular thermal shift assay; SPR, surface plasmon resonance; CNPY2, canopy FGF signaling regulator 2; ER, endoplasmic reticulum; PERK, protein kinase R-like endoplasmic reticulum kinase; CHOP, C/EBP homologous protein; co-IP, co-immunoprecipitation; STA, Schisantherin A; STC, Schisantherin C; dB SPL, decibels sound pressure level; EDTA, ethylenediaminetetraacetic acid; dB SPL, decibels sound pressure level; SGN, spiral ganglion neuron; IHCs, inner hair cells; OHCs, outer hair cells; CCK-8, Cell Counting Kit-8; OD, optical density; ODb, blank sample, ODc, control sample; NC, negative control; PVDF, polyvinylidene difluoride; RT, room temperature; LC-MS/MS, liquid chromatography tandem mass spectrometry; MS, mass spectrometry; DMSO, dimethyl sulfoxide; KDs, equilibrium dissociation constants; SP, standard precision; SEM, standard error of the mean; HSD, honestly significant difference; Ctrl, control group; CV, cell viability; Kd, dissociation rate constant; Ka, association rate constant; STS, sodium thiosulfate; UPR, unfolded protein response; BLB, blood-labyrinth barrier.
Apoptosis↗
Dermal changes in osteoporosis following prolonged treatment with human growth hormone.
Five patients with osteoporosis were treated with human growth hormone (hGH) for a year and the changes in their skin were studied by light and electron microscopy. The abnormally thin skin of osteoporosis appeared to change towards normal after treatment with hGH. There was a consistent proliferation of blood vessels, and increased number of mast cells and fibrocytes. The collagen bundles and elastic tissue fibers appeared hyperplastic and more horizontally oriented. The fine, vertical elastic fibrils of the papillary dermis had appeared decreased before treatment, but seemed to be restored to their normal configuration after treatment. Since there was no evidence of stimulation of hair, sebum, or melanin such as occurs in acromegaly, it is suggested that the scope of the direct action of hGH on the skin is limited to mesenchymal structures.
Aged↗
The removal and restitution of hair fat in the rat.
Castrated male rats were washed with a solution of sodium lauryl sulphate and warm water using a standard technique. Examination of samples of hair clipped from one flank showed that about 50% of the total ether-extractable hair fat was removed. The rate of restitution of hair fat was then measured by clipping a further sample from the opposite flank of each rat after an interval. The plateau level was restored in about 8 days. There was no significant correlation with body weight either of the plateau level in unwashed rats or of the rate of build-up of lipid in washed rats. This result provides no justification for correcting levels of hair lipid for body weight.
Animals↗
The sebotrophic action of growth hormone (BGH) in the rat.
Sebum production of rats was assessed by measuring the levels of fat extractable by diethyl ether from samples of hair clipped immediately after shampooing with sodium lauryl sulphate and 2 days later. By the use of matched litter mates in was unequivocally demonstrated that the response of the sebaceous glands to testosterone is virtually abolished by hypophysectomy and that it can be completely restored by pure bovine growth hormone.
Animals↗
Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition.
A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.
Adult↗
[The ultrastructure of the endings of nerve fibers of ordinary hairs of mammals under normal conditions and during degeneration and regeneration].
At ultrastructural level, three zones are distinguished of the palisade endings of nerve fibers, most of them in contact with the basement membrane of the outer epithelial sheath of the radix pili on rat muzzle. After division of the supplying nerve (n. infraorbitalis) in test animals of the same species, its nerve fibers and palisade endings undergo degeneration, followed by regeneration within 4-5 months. Changes in the ultrastructure of the mentioned nerve elements are thoroughly studied and demonstrated in the course of the two processes. While within 6...12 days of the operation, the palisade endings degenerate, 130 days after the intervention most of them are restored and exhibit an appreciable difference relative to their typical ultrastructure in normal state. The Schwann's cells processes, enveloping degenerated and regenerated palisade endings, similarly display marked fine-structure alterations.
Animals↗
An in vivo preparation (Thiry-Vella fistula) suitable for the measurement of intestinal absorption in the guinea pig.
A thiry-Vella isolated intestinal loop was constructed in the guinea pig. The procedure consisted of removal of a 30-cm segment of the jejunem, restoration of intestinal continuity by a jejunojejunostomy, and exteriorization of the segment through stomata sutured to the skin. The procedure was performed on seven guinea pigs of which three survived. The three survivors remained normal in maintenance of hair, feeding, and weight gain over a long period.
Animals↗
CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.
The transcription factor ATOH1 is a master regulator of mechanosensory hair-cell (HC) development in the ear. Here, we report that its target gene Casz1 regulates the maturation of outer HCs (OHCs). Genetic deletion of Casz1 during (but not after) cochlear development in the mouse caused: hearing loss; disorganization of mechanosensory stereocilia bundles in OHCs; reduced F-actin density in OHC cuticular plates; progressive OHC loss; and mild morphological alterations in inner HCs. This deletion also altered gene expression, delaying downregulation of genes expressed in immature OHCs, including the actin regulator-encoding gene Coro2a, and accelerating upregulation of genes expressed in mature OHCs. Deleting Coro2a in Casz1 mutant mice restored F-actin density in cuticular plates but increased stereocilia bundle disorganization and hearing thresholds, revealing that CORO2A provides an overall beneficial effect. Our data indicate that CASZ1 regulates transcriptional and morphological maturation of OHCs, and that CASZ1 in maturing HCs is necessary for hearing.
CASZ1↗
Burn alopecia.
Our experience in managing 117 patients with burn alopecia are presented. Most often we used staged excisions of the scarred scalp areas, and by this means we could cover up to 15 percent of the scalp. When the alopecia involved the anterior portion of the scalp, however, a rotational scalp flap was needed to restore the anterior hairline and/or sideburns. For those with burn alopecia of more than 60 percent of the scalp surface, no surgical treatment was effective; the women would often cover their scalps with hairpieces, but the men in our series preferred not to do so.
Adult↗
Gentamicin-induced changes in RNA content in sensory and ganglionic cells in the hearing organ of the lizard Calotes versicolor. A cytochemical and morphological investigation.
The effect of short-term administration of gentamicin on RNA content in isolated sensory and ganglionic cells in the hearing organ of the lizard Calotes versicolor was investigated. The effects of the drug on this biochemical parameter are compared with ultrastructural changes in sensory cells from the same material. In the first test group, daily intraperitoneal injections for 3 to 6 days resulted in a 30-50% decrease of the amount of RNA in sensory and ganglionic cells. No constant ultrastructural changes were recorded in the sensory cells at this point in time. A second test group received 3 or 5 injections of gentamicin and the animals were then left untreated for 21 days. The reduced RNA content persisted in both sensory cells and in ganglionic cells from animals that received 5 injections, whereas the content of RNA in ganglionic cells from lizards that received 3 injections was restored almost to control values at the end of this 21-day period. In the second test group, definite morphological derangements were observed in the sensory cells. The correlation between cytochemical and morphological findings as well as possible modes of action of gentamicin on inner ear ganglionic and sensory cell RNA content are discussed.
Animals↗
The small nucleolar RNA NON-CODING RNA 1 negatively regulates drought tolerance in Arabidopsis thaliana.
Small nucleolar RNAs (snoRNAs) function in ribosome biogenesis, and many ribosome biogenesis-related genes were downregulated by osmotic stress, implying a negative role of snoRNAs in drought tolerance. A snoRNA, namely, the NON-CODING RNA 1 (NCR1) was studied for its roles in drought tolerance in Arabidopsis. In comparison with wild-type (WT) plants, the loss-of-function ncr1 mutant plants showed enhanced drought tolerance, which was restored in the NCR1-complemented plants, whereas the NCR1-overexpressing plants revealed a drought-sensitive phenotype. Physiological analyses revealed that the ncr1 plants had a higher leaf surface temperature, lower water loss rates, and improved cell membrane integrity compared with WT. Comparative leaf transcriptomics and proteomics suggested that wax biosynthesis, anthocyanin metabolism, and leaf senescence processes are regulated by NCR1 under both normal and water-deficit conditions. Under drought, an increase in wax and anthocyanin accumulations and a delay in leaf senescence in ncr1 plants, when compared with WT, supported the transcriptome and proteomics data. Additionally, the ncr1 plants exhibited higher abscisic acid (ABA) sensitivity and longer root hairs than WT. Collectively, our results suggest that NCR1 negatively regulates drought tolerance through modification of wax biosynthesis, anthocyanin accumulation, leaf senescence, cell membrane integrity, ABA responses, and root hair development.
Arabidopsis↗
A quantitative study of C-mechanoreceptors in hairy skin of the cat.
1. Single C-mechanorecptor afferent units were examined by recording from fibres dissected from the saphenous nerves of cats anaesthetized with chloralose. The receptive fields, averaging 4 X 3 mm when 10-50 X threshold stimuli were used, were in the hairy skin of the leg and foot. 2. The extent and excitability of receptor terminals was tested by two-and three-point field studies. The excitability of terminals in one part of the field of a unit could be depressed without affecting the excitability of terminals elsewhere in the field. 3. The afferent units could be excited by both inward and outward movement of the stimulus probe, in appropriate conditions; that is, there was non-directional sensitivity. 4. After-discharge was found to depend on restorative movements of the skin, not on a persistence of the response of the receptor to the original movement. 5. The response to mechanical stimulation was slowly adapting with two time constants and the stimulus-response relationship was exactly described by a power function, with exponents ranging from 0-6 to 1-3. 6. The C-mechanoreceptors could be depressed by rapidly repeated or prolonged mechanical stimulation and the effect was confined to the excited terminals.
Action Potentials↗