The enormous diversity of hair fibers found in human population is striking, while the basic structure of human fibers is often the same! But why do some fibers curl? Curling is related to the machinery and processes that produce different keratin filament orientation in relation to the axis of hair growth, influenced by developmental and molecular control. It is established that a curly hair shaft is produced by a curved hair follicle that have an angulated dermal implantation, with a bulb bent in the shape of golf club, while the outer root sheath is dissymmetrical; have an outer side that is convex bulging and thin and a concave side in which the cells express alpha-smooth muscle protein reflecting internal mechanical force. Yet, the exact cause of hair curling is not known. All the previous studies were short of impacting curly hair treatment. My hypothesis is that the curling mechanical force is generated by a hypersensitive contracted Arrector Pili muscle (APM) of the hair follicle. In curly hair, each APM fiber is shortened; pulling its attachment spot upward towards the epidermis and obliquely or laterally; curling the outer root sheath to produce the curved follicle described above. This contraction has the influence at a time when the young hair root is being formed and keratin microfibrils are being oriented and packed. APM is a multi-unit muscle wherein each fiber contracts independently to create the enormous diversity of curly hair types. APM contraction can be modulated by oral administration of selective smooth muscle relaxing treatment that relax the curved follicle from within. Further studies are needed to confirm the role of APM in shaping curly hair follicle including AI studies, i.e., computer-aided target identification to demonstrate APM active site that can interact with herbal small molecules.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.